Epigenomic heterogeneity as a source of tumour evolution.

Ciriello, G. et al. Cancer evolution: a multifaceted affair. Cancer Discov. 14, 36–48 (2024).

doi: 10.1158/2159-8290.CD-23-0530 pubmed: 38047596

Marine, J.-C., Dawson, S.-J. & Dawson, M. A. Non-genetic mechanisms of therapeutic resistance in cancer. Nat. Rev. Cancer 20, 743–756 (2020).

doi: 10.1038/s41568-020-00302-4 pubmed: 33033407

Hanahan, D. Hallmarks of cancer: new dimensions. Cancer Discov. 12, 31–46 (2022).

doi: 10.1158/2159-8290.CD-21-1059 pubmed: 35022204

Rahme, G. J. et al. Modeling epigenetic lesions that cause gliomas. Cell 186, 3674–3685.e14 (2023).

doi: 10.1016/j.cell.2023.06.022 pubmed: 37494934 pmcid: 10530192

Gaudet, F. et al. Induction of tumors in mice by genomic hypomethylation. Science 300, 489–492 (2003).

doi: 10.1126/science.1083558 pubmed: 12702876

Parreno, V. et al. Transient loss of Polycomb components induces an epigenetic cancer fate. Nature 629, 688–696 (2024).

doi: 10.1038/s41586-024-07328-w pubmed: 38658752 pmcid: 11096130

Cimmino, L. et al. Restoration of TET2 function blocks aberrant self-renewal and leukemia progression. Cell 170, 1079–1095.e20 (2017).

doi: 10.1016/j.cell.2017.07.032 pubmed: 28823558 pmcid: 5755977

Mack, S. C. et al. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature 506, 445–450 (2014). This report describes a primary tumour arising and dependent solely on chromatin variants (as opposed to mutations).

doi: 10.1038/nature13108 pubmed: 24553142 pmcid: 4174313

Bertucci, F. et al. Genomic characterization of metastatic breast cancers. Nature 569, 560–564 (2019).

doi: 10.1038/s41586-019-1056-z pubmed: 31118521

Burdett, N. L. et al. Multiomic analysis of homologous recombination-deficient end-stage high-grade serous ovarian cancer. Nat. Genet. 55, 437–450 (2023). This paper demonstrates the mixed genetic and non-genetic evolution of metastatic ovarian cancer.

doi: 10.1038/s41588-023-01320-2 pubmed: 36849657

Makohon-Moore, A. P. et al. Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer. Nat. Genet. 49, 358–366 (2017).

doi: 10.1038/ng.3764 pubmed: 28092682 pmcid: 5663439

McDonald, O. G. et al. Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis. Nat. Genet. 49, 367–376 (2017).

doi: 10.1038/ng.3753 pubmed: 28092686 pmcid: 5695682

Preissl, S., Gaulton, K. J. & Ren, B. Characterizing cis-regulatory elements using single-cell epigenomics. Nat. Rev. Genet 24, 21–43 (2023).

doi: 10.1038/s41576-022-00509-1 pubmed: 35840754

Casado-Pelaez, M., Bueno-Costa, A. & Esteller, M. Single cell cancer epigenetics. Trends Cancer 8, 820–838 (2022).

doi: 10.1016/j.trecan.2022.06.005 pubmed: 35821003

Nam, A. S., Chaligne, R. & Landau, D. A. Integrating genetic and non-genetic determinants of cancer evolution by single-cell multi-omics. Nat. Rev. Genet. 22, 3–18 (2021).

doi: 10.1038/s41576-020-0265-5 pubmed: 32807900

Becker, W. R. et al. Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer. Nat. Genet. 54, 985–995 (2022). This multi-regional sampling study shows that a continuum of epigenomic-state transitions exist during tumorigenesis.

doi: 10.1038/s41588-022-01088-x pubmed: 35726067 pmcid: 9279149

Singh, H. et al. Hybrid stomach-intestinal chromatin states underlie human Barrett’s metaplasia. Gastroenterology 161, 924–939.e11 (2021).

doi: 10.1053/j.gastro.2021.05.057 pubmed: 34090884

Burdziak, C. et al. Epigenetic plasticity cooperates with cell-cell interactions to direct pancreatic tumorigenesis. Science 380, eadd5327 (2023). This report shows that heterogeneous cell states are primed for transformation through crosstalk with immune cells and chromatin remodelling.

doi: 10.1126/science.add5327 pubmed: 37167403 pmcid: 10316746

Wang, L. et al. The phenotypes of proliferating glioblastoma cells reside on a single axis of variation. Cancer Discov. 9, 1708–1719 (2019).

doi: 10.1158/2159-8290.CD-19-0329 pubmed: 31554641 pmcid: 7161589

Guilhamon, P. et al. Single-cell chromatin accessibility profiling of glioblastoma identifies an invasive cancer stem cell population associated with lower survival. eLife 10, e64090 (2021).

doi: 10.7554/eLife.64090 pubmed: 33427645 pmcid: 7847307

Wang, L. et al. A single-cell atlas of glioblastoma evolution under therapy reveals cell-intrinsic and cell-extrinsic therapeutic targets. Nat. Cancer 3, 1534–1552 (2022).

doi: 10.1038/s43018-022-00475-x pubmed: 36539501 pmcid: 9767870

Regner, M. J. et al. A multi-omic single-cell landscape of human gynecologic malignancies. Mol. Cell 81, 4924–4941.e10 (2021).

doi: 10.1016/j.molcel.2021.10.013 pubmed: 34739872

Terekhanova, N. V. et al. Epigenetic regulation during cancer transitions across 11 tumour types. Nature 623, 432–441 (2023).

doi: 10.1038/s41586-023-06682-5 pubmed: 37914932 pmcid: 10632147

Harpaz, N. et al. Single-cell epigenetic analysis reveals principles of chromatin states in H3.3-K27M gliomas. Mol. Cell 82, 2696–2713.e9 (2022).

doi: 10.1016/j.molcel.2022.05.023 pubmed: 35716669

Pixberg, C. F. et al. Analysis of DNA methylation in single circulating tumor cells. Oncogene 36, 3223–3231 (2017).

doi: 10.1038/onc.2016.480 pubmed: 28068321

Gkountela, S. et al. Circulating tumor cell clustering shapes DNA methylation to enable metastasis seeding. Cell 176, 98–112.e14 (2019).

doi: 10.1016/j.cell.2018.11.046 pubmed: 30633912 pmcid: 6363966

Chen, H. et al. Single-cell DNA methylome analysis of circulating tumor cells. Chin. J. Cancer Res. 33, 391–404 (2021).

doi: 10.21147/j.issn.1000-9604.2021.03.10 pubmed: 34321835 pmcid: 8286897

Cheow, L. F. et al. Single-cell multimodal profiling reveals cellular epigenetic heterogeneity. Nat. Methods 13, 833–836 (2016).

doi: 10.1038/nmeth.3961 pubmed: 27525975

Chaligne, R. et al. Epigenetic encoding, heritability and plasticity of glioma transcriptional cell states. Nat. Genet. 53, 1469–1479 (2021). This study showcases the use of single-cell multiomics to relate epigenomic changes to cell-state evolution.

doi: 10.1038/s41588-021-00927-7 pubmed: 34594037 pmcid: 8675181

Johnson, K. C. et al. Single-cell multimodal glioma analyses identify epigenetic regulators of cellular plasticity and environmental stress response. Nat. Genet. 53, 1456–1468 (2021). This study quantifies a DNA methylation disorder and its relationship to tumour evolution in glioma.

doi: 10.1038/s41588-021-00926-8 pubmed: 34594038 pmcid: 8570135

Satpathy, A. T. et al. Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion. Nat. Biotechnol. 37, 925–936 (2019). A large-scale scATAC-seq study of patient tumours that aims to understand the process of tumour evolution.

doi: 10.1038/s41587-019-0206-z pubmed: 31375813 pmcid: 7299161

Derrien, J. et al. Acquired resistance to a GPRC5D-directed T-cell engager in multiple myeloma is mediated by genetic or epigenetic target inactivation. Nat. Cancer 4, 1536–1543 (2023).

doi: 10.1038/s43018-023-00625-9 pubmed: 37653140

Wu, S. J. et al. Single-cell CUT&Tag analysis of chromatin modifications in differentiation and tumor progression. Nat. Biotechnol. 39, 819–824 (2021).

doi: 10.1038/s41587-021-00865-z pubmed: 33846646 pmcid: 8277750

Grosselin, K. et al. High-throughput single-cell ChIP–seq identifies heterogeneity of chromatin states in breast cancer. Nat. Genet. 51, 1060–1066 (2019).

doi: 10.1038/s41588-019-0424-9 pubmed: 31152164

Marsolier, J. et al. H3K27me3 conditions chemotolerance in triple-negative breast cancer. Nat. Genet. 54, 459–468 (2022). This study leverages histone modification profiles at single-cell resolution to propose a rationale for combining a histone demethylase inhibitor with chemotherapy to delay tumour recurrence.

doi: 10.1038/s41588-022-01047-6 pubmed: 35410383 pmcid: 7612638

Heumos, L. et al. Best practices for single-cell analysis across modalities. Nat. Rev. Genet. 24, 550–572 (2023).

doi: 10.1038/s41576-023-00586-w pubmed: 37002403

Baek, S. & Lee, I. Single-cell ATAC sequencing analysis: from data preprocessing to hypothesis generation. Comput. Struct. Biotechnol. J. 18, 1429–1439 (2020).

doi: 10.1016/j.csbj.2020.06.012 pubmed: 32637041 pmcid: 7327298

Marjanovic, N. D. et al. Emergence of a high-plasticity cell state during lung cancer evolution. Cancer Cell 38, 229–246.e13 (2020).

doi: 10.1016/j.ccell.2020.06.012 pubmed: 32707077 pmcid: 7745838

Cui, H. et al. scGPT: toward building a foundation model for single-cell multi-omics using generative AI. Nat. Methods 21, 1470–1480 (2024).

doi: 10.1038/s41592-024-02201-0 pubmed: 38409223

Teschendorff, A. E. & Enver, T. Single-cell entropy for accurate estimation of differentiation potency from a cell’s transcriptome. Nat. Commun. 8, 15599 (2017).

doi: 10.1038/ncomms15599 pubmed: 28569836 pmcid: 5461595

Landau, D. A. et al. Locally disordered methylation forms the basis of intratumor methylome variation in chronic lymphocytic leukemia. Cancer Cell 26, 813–825 (2014).

doi: 10.1016/j.ccell.2014.10.012 pubmed: 25490447 pmcid: 4302418

Chan, J. M. et al. Lineage plasticity in prostate cancer depends on JAK/STAT inflammatory signaling. Science 377, 1180–1191 (2022). This report reveals that lineage plasticity in prostate cancer is responsible for resistance to antiandrogen receptor therapy.

doi: 10.1126/science.abn0478 pubmed: 35981096 pmcid: 9653178

Tedesco, M. et al. Chromatin velocity reveals epigenetic dynamics by single-cell profiling of heterochromatin and euchromatin. Nat. Biotechnol. 40, 235–244 (2022).

doi: 10.1038/s41587-021-01031-1 pubmed: 34635836

Bartosovic, M. & Castelo-Branco, G. Multimodal chromatin profiling using nanobody-based single-cell CUT&Tag. Nat. Biotechnol. 41, 794–805 (2023).

doi: 10.1038/s41587-022-01535-4 pubmed: 36536148

Xiong, H., Wang, Q., Li, C. C. & He, A. Single-cell joint profiling of multiple epigenetic proteins and gene transcription. Sci. Adv. 10, eadi3664 (2024).

doi: 10.1126/sciadv.adi3664 pubmed: 38170774 pmcid: 10796078

Lochs, S. J. A. et al. Combinatorial single-cell profiling of major chromatin types with MAbID. Nat. Methods 21, 72–82 (2024).

doi: 10.1038/s41592-023-02090-9 pubmed: 38049699

Füllgrabe, J. et al. Simultaneous sequencing of genetic and epigenetic bases in DNA. Nat. Biotechnol. 41, 1457–1464 (2023).

doi: 10.1038/s41587-022-01652-0 pubmed: 36747096 pmcid: 10567558

Hou, Y. et al. Single-cell triple omics sequencing reveals genetic, epigenetic, and transcriptomic heterogeneity in hepatocellular carcinomas. Cell Res. 26, 304–319 (2016).

doi: 10.1038/cr.2016.23 pubmed: 26902283 pmcid: 4783472

Bian, S. et al. Single-cell multiomics sequencing and analyses of human colorectal cancer. Science 362, 1060–1063 (2018).

doi: 10.1126/science.aao3791 pubmed: 30498128

Mazor, T. et al. DNA methylation and somatic mutations converge on cell cycle and define similar evolutionary histories in brain tumors. Cancer Cell 28, 307–317 (2015).

doi: 10.1016/j.ccell.2015.07.012 pubmed: 26373278 pmcid: 4573399

Brocks, D. et al. Intratumor DNA methylation heterogeneity reflects clonal evolution in aggressive prostate cancer. Cell Rep. 8, 798–806 (2014).

doi: 10.1016/j.celrep.2014.06.053 pubmed: 25066126

Gaiti, F. et al. Epigenetic evolution and lineage histories of chronic lymphocytic leukaemia. Nature 569, 576–580 (2019).

doi: 10.1038/s41586-019-1198-z pubmed: 31092926 pmcid: 6533116

Lareau, C. A. et al. Massively parallel single-cell mitochondrial DNA genotyping and chromatin profiling. Nat. Biotechnol. 39, 451–461 (2021).

doi: 10.1038/s41587-020-0645-6 pubmed: 32788668

Wagner, D. E. & Klein, A. M. Lineage tracing meets single-cell omics: opportunities and challenges. Nat. Rev. Genet. 21, 410–427 (2020).

doi: 10.1038/s41576-020-0223-2 pubmed: 32235876 pmcid: 7307462

Sankaran, V. G., Weissman, J. S. & Zon, L. I. Cellular barcoding to decipher clonal dynamics in disease. Science 378, eabm5874 (2022).

doi: 10.1126/science.abm5874 pubmed: 36227997 pmcid: 10111813

Serrano, A., Berthelet, J., Naik, S. H. & Merino, D. Mastering the use of cellular barcoding to explore cancer heterogeneity. Nat. Rev. Cancer 22, 609–624 (2022).

doi: 10.1038/s41568-022-00500-2 pubmed: 35982229

Nadalin, F. et al. Multi-omic lineage tracing predicts the transcriptional, epigenetic and genetic determinants of cancer evolution. Nat. Commun. 15, 7609 (2023).

doi: 10.1038/s41467-024-51424-4

Rovira-Clavé, X. et al. Spatial epitope barcoding reveals clonal tumor patch behaviors. Cancer Cell 40, 1423–1439.e11 (2022).

doi: 10.1016/j.ccell.2022.09.014 pubmed: 36240778 pmcid: 9673683

Dhainaut, M. et al. Spatial CRISPR genomics identifies regulators of the tumor microenvironment. Cell 185, 1223–1239.e20 (2022).

doi: 10.1016/j.cell.2022.02.015 pubmed: 35290801 pmcid: 8992964

Deng, Y. et al. Spatial-CUT&Tag: spatially resolved chromatin modification profiling at the cellular level. Science 375, 681–686 (2022).

doi: 10.1126/science.abg7216 pubmed: 35143307 pmcid: 7612972

Hagemann-Jensen, M. et al. Single-cell RNA counting at allele and isoform resolution using Smart-seq3. Nat. Biotechnol. 38, 708–714 (2020).

doi: 10.1038/s41587-020-0497-0 pubmed: 32518404

Takayama, N. et al. The transition from quiescent to activated states in human hematopoietic stem cells is governed by dynamic 3D genome reorganization. Cell Stem Cell 28, 488–501.e10 (2021).

doi: 10.1016/j.stem.2020.11.001 pubmed: 33242413

Llorens-Bobadilla, E. et al. Solid-phase capture and profiling of open chromatin by spatial ATAC. Nat. Biotechnol. 41, 1085–1088 (2023).

doi: 10.1038/s41587-022-01603-9 pubmed: 36604544 pmcid: 10421738

Noberini, R. et al. Spatial epi-proteomics enabled by histone post-translational modification analysis from low-abundance clinical samples. Clin. Epigenetics 13, 145 (2021).

doi: 10.1186/s13148-021-01120-7 pubmed: 34315505 pmcid: 8317427

Lu, T., Ang, C. E. & Zhuang, X. Spatially resolved epigenomic profiling of single cells in complex tissues. Cell 185, 4448–4464.e17 (2022).

doi: 10.1016/j.cell.2022.09.035 pubmed: 36272405 pmcid: 9691621

Deng, Y. et al. Spatial profiling of chromatin accessibility in mouse and human tissues. Nature 609, 375–383 (2022).

doi: 10.1038/s41586-022-05094-1 pubmed: 35978191 pmcid: 9452302

Kind, J. et al. Genome-wide maps of nuclear lamina interactions in single human cells. Cell 163, 134–147 (2015).

doi: 10.1016/j.cell.2015.08.040 pubmed: 26365489 pmcid: 4583798

Ramani, V. et al. Massively multiplex single-cell Hi-C. Nat. Methods 14, 263–266 (2017).

doi: 10.1038/nmeth.4155 pubmed: 28135255 pmcid: 5330809

Pott, S. Simultaneous measurement of chromatin accessibility, DNA methylation, and nucleosome phasing in single cells. eLife 6, e23203 (2017).

doi: 10.7554/eLife.23203 pubmed: 28653622 pmcid: 5487215

Dentro, S. C. et al. Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes. Cell 184, 2239–2254.e39 (2021).

doi: 10.1016/j.cell.2021.03.009 pubmed: 33831375 pmcid: 8054914

Jamal-Hanjani, M. et al. Tracking the evolution of non-small-cell lung cancer. N. Engl. J. Med 376, 2109–2121 (2017).

doi: 10.1056/NEJMoa1616288 pubmed: 28445112

Espinoza Pereira, K. N., Shan, J., Licht, J. D. & Bennett, R. L. Histone mutations in cancer. Biochem. Soc. Trans. 51, 1749–1763 (2023).

doi: 10.1042/BST20210567 pubmed: 37721138 pmcid: 10657182

Turajlic, S. et al. Tracking cancer evolution reveals constrained routes to metastases: TRACERx Renal. Cell 173, 581–594.e12 (2018).

doi: 10.1016/j.cell.2018.03.057 pubmed: 29656895 pmcid: 5938365

Janssens, D. H. et al. Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia. Nat. Genet. 53, 1586–1596 (2021).

doi: 10.1038/s41588-021-00941-9 pubmed: 34663924 pmcid: 8571097

Béguelin, W. et al. EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation. Cancer Cell 23, 677–692 (2013).

doi: 10.1016/j.ccr.2013.04.011 pubmed: 23680150 pmcid: 3681809

Loukas, I. et al. Selective advantage of epigenetically disrupted cancer cells via phenotypic inertia. Cancer Cell 41, 70–87.e14 (2022).

doi: 10.1016/j.ccell.2022.10.002 pubmed: 36332625

Heide, T. et al. The co-evolution of the genome and epigenome in colorectal cancer. Nature 611, 733–743 (2022).

doi: 10.1038/s41586-022-05202-1 pubmed: 36289335 pmcid: 9684080

Lambuta, R. A. et al. Whole-genome doubling drives oncogenic loss of chromatin segregation. Nature 615, 925–933 (2023).

doi: 10.1038/s41586-023-05794-2 pubmed: 36922594 pmcid: 10060163

Roehrig, A. et al. Single-cell multiomics reveals the interplay of clonal evolution and cellular plasticity in hepatoblastoma. Nat. Commun. 15, 3031 (2024).

doi: 10.1038/s41467-024-47280-x pubmed: 38589411 pmcid: 11001886

Pavlova, N. N., Zhu, J. & Thompson, C. B. The hallmarks of cancer metabolism: still emerging. Cell Metab. 34, 355–377 (2022).

doi: 10.1016/j.cmet.2022.01.007 pubmed: 35123658 pmcid: 8891094

Dai, Z., Ramesh, V. & Locasale, J. W. The evolving metabolic landscape of chromatin biology and epigenetics. Nat. Rev. Genet. 21, 737–753 (2020).

doi: 10.1038/s41576-020-0270-8 pubmed: 32908249 pmcid: 8059378

Deblois, G. et al. Epigenetic switch-induced viral mimicry evasion in chemotherapy-resistant breast cancer. Cancer Discov. 10, 1312–1329 (2020). This paper describes the use of an EZH2 inhibitor combined with chemotherapy to resensitize a treatment-resistant tumour.

doi: 10.1158/2159-8290.CD-19-1493 pubmed: 32546577

Chakraborty, A. A. et al. Histone demethylase KDM6A directly senses oxygen to control chromatin and cell fate. Science 363, 1217–1222 (2019).

doi: 10.1126/science.aaw1026 pubmed: 30872525 pmcid: 7336390

Batie, M. et al. Hypoxia induces rapid changes to histone methylation and reprograms chromatin. Science 363, 1222–1226 (2019).

doi: 10.1126/science.aau5870 pubmed: 30872526

Thienpont, B. et al. Tumour hypoxia causes DNA hypermethylation by reducing TET activity. Nature 537, 63–68 (2016).

doi: 10.1038/nature19081 pubmed: 27533040 pmcid: 5133388

Michealraj, K. A. et al. Metabolic regulation of the epigenome drives lethal infantile ependymoma. Cell 181, 1329–1345.e24 (2020).

doi: 10.1016/j.cell.2020.04.047 pubmed: 32445698 pmcid: 10782558

Vaz, M. et al. Chronic cigarette smoke-induced epigenomic changes precede sensitization of bronchial epithelial cells to single-step transformation by KRAS mutations. Cancer Cell 32, 360–376.e6 (2017).

doi: 10.1016/j.ccell.2017.08.006 pubmed: 28898697 pmcid: 5596892

Abu-Remaileh, M. et al. Chronic inflammation induces a novel epigenetic program that is conserved in intestinal adenomas and in colorectal cancer. Cancer Res. 75, 2120–2130 (2015).

doi: 10.1158/0008-5472.CAN-14-3295 pubmed: 25808873

Hansen, K. D. et al. Increased methylation variation in epigenetic domains across cancer types. Nat. Genet. 43, 768–775 (2011).

doi: 10.1038/ng.865 pubmed: 21706001 pmcid: 3145050

Jenkinson, G., Pujadas, E., Goutsias, J. & Feinberg, A. P. Potential energy landscapes identify the information-theoretic nature of the epigenome. Nat. Genet. 49, 719–729 (2017).

doi: 10.1038/ng.3811 pubmed: 28346445 pmcid: 5565269

Fraga, M. F. et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc. Natl Acad. Sci. USA 102, 10604–10609 (2005).

doi: 10.1073/pnas.0500398102 pubmed: 16009939 pmcid: 1174919

Tao, Y. et al. Aging-like spontaneous epigenetic silencing facilitates Wnt activation, stemness, and Braf

doi: 10.1016/j.ccell.2019.01.005 pubmed: 30753828 pmcid: 6636642

Scherer, M. et al. Somatic epimutations enable single-cell lineage tracing in native hematopoiesis across the murine and human lifespan. Preprint at bioRxiv https://doi.org/10.1101/2024.04.01.587514 (2024).

Almouzni, G. & Cedar, H. Maintenance of epigenetic information. Cold Spring Harb. Perspect. Biol. 8, a019372 (2016).

doi: 10.1101/cshperspect.a019372 pubmed: 27141050 pmcid: 4852805

Endicott, J. L., Nolte, P. A., Shen, H. & Laird, P. W. Cell division drives DNA methylation loss in late-replicating domains in primary human cells. Nat. Commun. 13, 6659 (2022).

doi: 10.1038/s41467-022-34268-8 pubmed: 36347867 pmcid: 9643452

Thomas, S. L. et al. DNA strand asymmetry generated by CpG hemimethylation has opposing effects on CTCF binding. Nucleic Acids Res. 51, 5997–6005 (2023).

doi: 10.1093/nar/gkad293 pubmed: 37094063 pmcid: 10325916

Xu, C. & Corces, V. G. Nascent DNA methylome mapping reveals inheritance of hemimethylation at CTCF/cohesin sites. Science 359, 1166–1170 (2018).

doi: 10.1126/science.aan5480 pubmed: 29590048 pmcid: 6359960

Papathanasiou, S. et al. Heritable transcriptional defects from aberrations of nuclear architecture. Nature 619, 184–192 (2023).

doi: 10.1038/s41586-023-06157-7 pubmed: 37286600 pmcid: 10322708

Agustinus, A. S. et al. Epigenetic dysregulation from chromosomal transit in micronuclei. Nature 619, 176–183 (2023). Together with Papathanasiou et al. (2023), this paper reveals a role for micronuclei in the stochastic acquisition of chromatin variants.

doi: 10.1038/s41586-023-06084-7 pubmed: 37286593 pmcid: 10322720

Burgess, R. J. & Zhang, Z. Histone chaperones in nucleosome assembly and human disease. Nat. Struct. Mol. Biol. 20, 14–22 (2013).

doi: 10.1038/nsmb.2461 pubmed: 23288364 pmcid: 4004355

Yang, J.-H. et al. Loss of epigenetic information as a cause of mammalian aging. Cell 186, 305–326.e27 (2023).

doi: 10.1016/j.cell.2022.12.027 pubmed: 36638792 pmcid: 10166133

Flavahan, W. A., Gaskell, E. & Bernstein, B. E. Epigenetic plasticity and the hallmarks of cancer. Science 357, eaal2380 (2017).

doi: 10.1126/science.aal2380 pubmed: 28729483 pmcid: 5940341

Feinberg, A. P. & Levchenko, A. Epigenetics as a mediator of plasticity in cancer. Science 379, eaaw3835 (2023).

doi: 10.1126/science.aaw3835 pubmed: 36758093 pmcid: 10249049

Waddington, C. H. The Strategy of the Genes: a Discussion of Some Aspects of Theoretical Biology (Allen & Unwin, 1957).

Teschendorff, A. E. & Feinberg, A. P. Statistical mechanics meets single-cell biology. Nat. Rev. Genet. 22, 459–476 (2021).

doi: 10.1038/s41576-021-00341-z pubmed: 33875884 pmcid: 10152720

Shaffer, S. M. et al. Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance. Nature 546, 431–435 (2017).

doi: 10.1038/nature22794 pubmed: 28607484 pmcid: 5542814

Nguyen, A., Yoshida, M., Goodarzi, H. & Tavazoie, S. F. Highly variable cancer subpopulations that exhibit enhanced transcriptome variability and metastatic fitness. Nat. Commun. 7, 11246 (2016).

doi: 10.1038/ncomms11246 pubmed: 27138336 pmcid: 4857405

Yang, D. et al. Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution. Cell 185, 1905–1923.e25 (2022).

doi: 10.1016/j.cell.2022.04.015 pubmed: 35523183 pmcid: 9452598

Bala, P. et al. Aberrant cell state plasticity mediated by developmental reprogramming precedes colorectal cancer initiation. Sci. Adv. 9, eadf0927 (2023).

doi: 10.1126/sciadv.adf0927 pubmed: 36989360 pmcid: 10058311

Fennell, K. A. et al. Non-genetic determinants of malignant clonal fitness at single-cell resolution. Nature 601, 125–131 (2022).

doi: 10.1038/s41586-021-04206-7 pubmed: 34880496

Franzetti, G.-A. et al. Cell-to-cell heterogeneity of EWSR1-FLI1 activity determines proliferation/migration choices in Ewing sarcoma cells. Oncogene 36, 3505–3514 (2017).

doi: 10.1038/onc.2016.498 pubmed: 28135250 pmcid: 5541267

Puisieux, A., Pommier, R. M., Morel, A.-P. & Lavial, F. Cellular pliancy and the multistep process of tumorigenesis. Cancer Cell 33, 164–172 (2018).

doi: 10.1016/j.ccell.2018.01.007 pubmed: 29438693

Small, E. J. et al. Characterization of neuroendocrine prostate cancer (NEPC) in patients with metastatic castration resistant prostate cancer (mCRPC) resistant to abiraterone (Abi) or enzalutamide (Enz): preliminary results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT). J. Clin. Oncol. 33, 5003 (2015).

doi: 10.1200/jco.2015.33.15_suppl.5003

Tang, F. et al. Chromatin profiles classify castration-resistant prostate cancers suggesting therapeutic targets. Science 376, eabe1505 (2022).

doi: 10.1126/science.abe1505 pubmed: 35617398 pmcid: 9299269

Ku, S. Y. et al. Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. Science 355, 78–83 (2017).

doi: 10.1126/science.aah4199 pubmed: 28059767 pmcid: 5367887

Mu, P. et al. SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer. Science 355, 84–88 (2017).

doi: 10.1126/science.aah4307 pubmed: 28059768 pmcid: 5247742

Zou, M. et al. Transdifferentiation as a mechanism of treatment resistance in a mouse model of castration-resistant prostate cancer. Cancer Discov. 7, 736–749 (2017).

doi: 10.1158/2159-8290.CD-16-1174 pubmed: 28411207 pmcid: 5501744

Magnani, L. et al. Genome-wide reprogramming of the chromatin landscape underlies endocrine therapy resistance in breast cancer. Proc. Natl Acad. Sci. USA 110, E1490–E1499 (2013).

doi: 10.1073/pnas.1219992110 pubmed: 23576735 pmcid: 3631697

Rosano, D. et al. Long-term multimodal recording reveals epigenetic adaptation routes in dormant breast cancer cells. Cancer Discov. 14, 866–889 (2024).

doi: 10.1158/2159-8290.CD-23-1161 pubmed: 38527495 pmcid: 11061610

Magnani, L., Ballantyne, E. B., Zhang, X. & Lupien, M. PBX1 genomic pioneer function drives ERα signaling underlying progression in breast cancer. PLoS Genet. 7, e1002368 (2011).

doi: 10.1371/journal.pgen.1002368 pubmed: 22125492 pmcid: 3219601

Teng, M., Zhou, S., Cai, C., Lupien, M. & He, H. H. Pioneer of prostate cancer: past, present and the future of FOXA1. Protein Cell 12, 29–38 (2021).

doi: 10.1007/s13238-020-00786-8 pubmed: 32946061

Zhang, Y. et al. Nucleation of DNA repair factors by FOXA1 links DNA demethylation to transcriptional pioneering. Nat. Genet. 48, 1003–1013 (2016).

doi: 10.1038/ng.3635 pubmed: 27500525

Huyghe, A., Trajkova, A. & Lavial, F. Cellular plasticity in reprogramming, rejuvenation and tumorigenesis: a pioneer TF perspective. Trends Cell Biol. 34, 255–267 (2023).

doi: 10.1016/j.tcb.2023.07.013 pubmed: 37648593

Lindner, P. et al. EMT transcription factor ZEB1 alters the epigenetic landscape of colorectal cancer cells. Cell Death Dis. 11, 147 (2020).

doi: 10.1038/s41419-020-2340-4 pubmed: 32094334 pmcid: 7040187

De Cock, J. M. et al. Inflammation triggers Zeb1-dependent escape from tumor latency. Cancer Res. 76, 6778–6784 (2016).

doi: 10.1158/0008-5472.CAN-16-0608 pubmed: 27530323 pmcid: 5135644

Chaffer, C. L. et al. Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell 154, 61–74 (2013).

doi: 10.1016/j.cell.2013.06.005 pubmed: 23827675 pmcid: 4015106

Falvo, D. J. et al. A reversible epigenetic memory of inflammatory injury controls lineage plasticity and tumor initiation in the mouse pancreas. Dev. Cell 58, 2959–2973.e7 (2023).

doi: 10.1016/j.devcel.2023.11.008 pubmed: 38056453

Gonzales, K. A. U. et al. Stem cells expand potency and alter tissue fitness by accumulating diverse epigenetic memories. Science 374, eabh2444 (2021).

doi: 10.1126/science.abh2444 pubmed: 34822296 pmcid: 8896201

Alonso-Curbelo, D. et al. A gene–environment-induced epigenetic program initiates tumorigenesis. Nature 590, 642–648 (2021). This study showcases the interplay between genetic and chromatin variants occurring in transformation.

doi: 10.1038/s41586-020-03147-x pubmed: 33536616 pmcid: 8482641

Del Poggetto, E. et al. Epithelial memory of inflammation limits tissue damage while promoting pancreatic tumorigenesis. Science 373, eabj0486 (2021).

doi: 10.1126/science.abj0486 pubmed: 34529467 pmcid: 9733946

LaFave, L. M. et al. Epigenomic state transitions characterize tumor progression in mouse lung adenocarcinoma. Cancer Cell 38, 212–228.e13 (2020).

doi: 10.1016/j.ccell.2020.06.006 pubmed: 32707078 pmcid: 7641015

Levra Levron, C. et al. Tissue memory relies on stem cell priming in distal undamaged areas. Nat. Cell Biol. 25, 740–753 (2023).

doi: 10.1038/s41556-023-01120-0 pubmed: 37081165 pmcid: 10185470

Karras, P. et al. A cellular hierarchy in melanoma uncouples growth and metastasis. Nature 610, 190–198 (2022).

doi: 10.1038/s41586-022-05242-7 pubmed: 36131018 pmcid: 10439739

Chang, C. A. et al. Ontogeny and vulnerabilities of drug-tolerant persisters in HER2

doi: 10.1158/2159-8290.CD-20-1265 pubmed: 34911733 pmcid: 8983469

Dhimolea, E. et al. An embryonic diapause-like adaptation with suppressed Myc activity enables tumor treatment persistence. Cancer Cell 39, 240–256.e11 (2021).

doi: 10.1016/j.ccell.2020.12.002 pubmed: 33417832 pmcid: 8670073

Rehman, S. K. et al. Colorectal cancer cells enter a diapause-like DTP state to survive chemotherapy. Cell 184, 226–242.e21 (2021).

doi: 10.1016/j.cell.2020.11.018 pubmed: 33417860

Oren, Y. et al. Cycling cancer persister cells arise from lineages with distinct programs. Nature 596, 576–582 (2021).

doi: 10.1038/s41586-021-03796-6 pubmed: 34381210 pmcid: 9209846

Ramirez, M. et al. Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells. Nat. Commun. 7, 10690 (2016).

doi: 10.1038/ncomms10690 pubmed: 26891683 pmcid: 4762880

Goyal, Y. et al. Diverse clonal fates emerge upon drug treatment of homogeneous cancer cells. Nature 620, 651–659 (2023).

doi: 10.1038/s41586-023-06342-8 pubmed: 37468627 pmcid: 10628994

Morel, D., Jeffery, D., Aspeslagh, S., Almouzni, G. & Postel-Vinay, S. Combining epigenetic drugs with other therapies for solid tumours — past lessons and future promise. Nat. Rev. Clin. Oncol. 17, 91–107 (2020).

doi: 10.1038/s41571-019-0267-4 pubmed: 31570827

Abou-Alfa, G. K. et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 21, 796–807 (2020).

doi: 10.1016/S1470-2045(20)30157-1 pubmed: 32416072 pmcid: 7523268

Gounder, M. et al. Tazemetostat in advanced epithelioid sarcoma with loss of INI1/SMARCB1: an international, open-label, phase 2 basket study. Lancet Oncol. 21, 1423–1432 (2020).

doi: 10.1016/S1470-2045(20)30451-4 pubmed: 33035459

Schrump, D. S. et al. Phase I study of decitabine-mediated gene expression in patients with cancers involving the lungs, esophagus, or pleura. Clin. Cancer Res. 12, 5777–5785 (2006).

doi: 10.1158/1078-0432.CCR-06-0669 pubmed: 17020984

Jones, P. A., Ohtani, H., Chakravarthy, A. & De Carvalho, D. D. Epigenetic therapy in immune-oncology. Nat. Rev. Cancer 19, 151–161 (2019).

doi: 10.1038/s41568-019-0109-9 pubmed: 30723290

Matei, D. et al. Epigenetic resensitization to platinum in ovarian cancer. Cancer Res. 72, 2197–2205 (2012).

doi: 10.1158/0008-5472.CAN-11-3909 pubmed: 22549947 pmcid: 3700422

Jiang, Z. et al. Tucidinostat plus exemestane for postmenopausal patients with advanced, hormone receptor-positive breast cancer (ACE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 20, 806–815 (2019).

doi: 10.1016/S1470-2045(19)30164-0 pubmed: 31036468

Murphy, A. G. et al. Epigenetic priming prior to pembrolizumab in mismatch repair-proficient advanced colorectal cancer. J. Clin. Oncol. 37, 591 (2019).

doi: 10.1200/JCO.2019.37.4_suppl.591

Hicks, K. C. et al. Epigenetic priming of both tumor and NK cells augments antibody-dependent cellular cytotoxicity elicited by the anti-PD-L1 antibody avelumab against multiple carcinoma cell types. Oncoimmunology 7, e1466018 (2018).

doi: 10.1080/2162402X.2018.1466018 pubmed: 30377559 pmcid: 6205056

Chiappinelli, K. B. et al. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 162, 974–986 (2015).

doi: 10.1016/j.cell.2015.07.011 pubmed: 26317466 pmcid: 4556003

Roulois, D. et al. DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell 162, 961–973 (2015). Together with Chiappinelli et al. (2015), this paper provides a rationale for combining epigenetic approaches and immunotherapies in cancer.

doi: 10.1016/j.cell.2015.07.056 pubmed: 26317465 pmcid: 4843502

Topper, M. J., Vaz, M., Marrone, K. A., Brahmer, J. R. & Baylin, S. B. The emerging role of epigenetic therapeutics in immuno-oncology. Nat. Rev. Clin. Oncol. 17, 75–90 (2020).

doi: 10.1038/s41571-019-0266-5 pubmed: 31548600

Hogg, S. J., Beavis, P. A., Dawson, M. A. & Johnstone, R. W. Targeting the epigenetic regulation of antitumour immunity. Nat. Rev. Drug Discov. 19, 776–800 (2020).

doi: 10.1038/s41573-020-0077-5 pubmed: 32929243

Hangauer, M. J. et al. Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition. Nature 551, 247–250 (2017).

doi: 10.1038/nature24297 pubmed: 29088702 pmcid: 5933935

Viswanathan, V. S. et al. Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway. Nature 547, 453–457 (2017).

doi: 10.1038/nature23007 pubmed: 28678785 pmcid: 5667900

Fong, C. Y. et al. BET inhibitor resistance emerges from leukaemia stem cells. Nature 525, 538–542 (2015).

doi: 10.1038/nature14888 pubmed: 26367796 pmcid: 6069604

Sharma, S. V. et al. A chromatin-mediated reversible drug tolerant state in cancer cell subpopulations. Cell 141, 69–80 (2010). This work provides a rationale for combining epigenetic compounds with cancer therapies to prevent drug tolerance.

doi: 10.1016/j.cell.2010.02.027 pubmed: 20371346 pmcid: 2851638

Vinogradova, M. et al. An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer cells. Nat. Chem. Biol. 12, 531–538 (2016).

doi: 10.1038/nchembio.2085 pubmed: 27214401

Liau, B. B. et al. Adaptive chromatin remodeling drives glioblastoma stem cell plasticity and drug tolerance. Cell Stem Cell 20, 233–246.e7 (2017).

doi: 10.1016/j.stem.2016.11.003 pubmed: 27989769

Rambow, F. et al. Toward minimal residual disease-directed therapy in melanoma. Cell 174, 843–855.e19 (2018).

doi: 10.1016/j.cell.2018.06.025 pubmed: 30017245

Bell, C. C. et al. Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia. Nat. Commun. 10, 2723 (2019).

doi: 10.1038/s41467-019-10652-9 pubmed: 31222014 pmcid: 6586637

Hinohara, K. et al. KDM5 histone demethylase activity links cellular transcriptomic heterogeneity to therapeutic resistance. Cancer Cell 34, 939–953.e9 (2018).

doi: 10.1016/j.ccell.2018.10.014 pubmed: 30472020 pmcid: 6310147

Webb, T., Craigon, C. & Ciulli, A. Targeting epigenetic modulators using PROTAC degraders: current status and future perspective. Bioorg. Med. Chem. Lett. 63, 128653 (2022).

doi: 10.1016/j.bmcl.2022.128653 pubmed: 35257896

Milazzo, F. M. et al. ErbB2 targeted epigenetic modulation: anti-tumor efficacy of the ADC trastuzumab-HDACi ST8176AA1. Front. Oncol. 9, 1534 (2019).

doi: 10.3389/fonc.2019.01534 pubmed: 32039017

Cini, E. et al. Antibody drug conjugates (ADCs) charged with HDAC inhibitor for targeted epigenetic modulation. Chem. Sci. 9, 6490–6496 (2018).

doi: 10.1039/C7SC05266A pubmed: 30288233 pmcid: 6144071

Stunnenberg, H. G. et al. The International Human Epigenome Consortium: a blueprint for scientific collaboration and discovery. Cell 167, 1145–1149 (2016).

doi: 10.1016/j.cell.2016.11.007 pubmed: 27863232

Landau, D.-A. et al. Increased local disorder of DNA methylation forms the basis of high intra-leukemic epigenetic heterogeneity and enhances CLL evolution. Blood 122, 596 (2013).

doi: 10.1182/blood.V122.21.596.596

Guo, H. et al. Single-cell methylome landscapes of mouse embryonic stem cells and early embryos analyzed using reduced representation bisulfite sequencing. Genome Res. 23, 2126–2135 (2013).

doi: 10.1101/gr.161679.113 pubmed: 24179143 pmcid: 3847781

Smallwood, S. A. et al. Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity. Nat. Methods 11, 817–820 (2014).

doi: 10.1038/nmeth.3035 pubmed: 25042786 pmcid: 4117646

Farlik, M. et al. Single-cell DNA methylome sequencing and bioinformatic inference of epigenomic cell-state dynamics. Cell Rep. 10, 1386–1397 (2015).

doi: 10.1016/j.celrep.2015.02.001 pubmed: 25732828 pmcid: 4542311

Han, L. et al. Bisulfite-independent analysis of CpG island methylation enables genome-scale stratification of single cells. Nucleic Acids Res. 45, e77 (2017).

pubmed: 28126923 pmcid: 5605247

Shareef, S. J. et al. Extended-representation bisulfite sequencing of gene regulatory elements in multiplexed samples and single cells. Nat. Biotechnol. 39, 1086–1094 (2021).

doi: 10.1038/s41587-021-00910-x pubmed: 33958785 pmcid: 8434949

Grants, J. M. et al. Altered microRNA expression links IL6 and TNF-induced inflammaging with myeloid malignancy in humans and mice. Blood 135, 2235–2251 (2020).

doi: 10.1182/blood.2019003105 pubmed: 32384151

Meir, Z., Mukamel, Z., Chomsky, E., Lifshitz, A. & Tanay, A. Single-cell analysis of clonal maintenance of transcriptional and epigenetic states in cancer cells. Nat. Genet. 52, 709–718 (2020).

doi: 10.1038/s41588-020-0645-y pubmed: 32601473 pmcid: 7610382

Huang, K. K. et al. Genomic and epigenomic profiling of high-risk intestinal metaplasia reveals molecular determinants of progression to gastric cancer. Cancer Cell 33, 137–150.e5 (2018).

doi: 10.1016/j.ccell.2017.11.018 pubmed: 29290541

Niemöller, C. et al. Bisulfite-free epigenomics and genomics of single cells through methylation-sensitive restriction. Commun. Biol. 4, 153 (2021).

doi: 10.1038/s42003-021-01661-w pubmed: 33526904 pmcid: 7851132

Hunt, K. V. et al. scTEM-seq: single-cell analysis of transposable element methylation to link global epigenetic heterogeneity with transcriptional programs. Sci. Rep. 12, 5776 (2022).

doi: 10.1038/s41598-022-09765-x pubmed: 35388081 pmcid: 8986802

Akhtar-Zaidi, B. et al. Epigenomic enhancer profiling defines a signature of colon cancer. Science 336, 736–739 (2012).

doi: 10.1126/science.1217277 pubmed: 22499810 pmcid: 3711120

Corces, M. R. et al. The chromatin accessibility landscape of primary human cancers. Science 362, eaav1898 (2018).

doi: 10.1126/science.aav1898 pubmed: 30361341 pmcid: 6408149

Buenrostro, J. D. et al. Single-cell chromatin accessibility reveals principles of regulatory variation. Nature 523, 486–490 (2015).

doi: 10.1038/nature14590 pubmed: 26083756 pmcid: 4685948

Cusanovich, D. A. et al. Multiplex single cell profiling of chromatin accessibility by combinatorial cellular indexing. Science 348, 910–914 (2015).

doi: 10.1126/science.aab1601 pubmed: 25953818 pmcid: 4836442

Xu, K. et al. Single-cell RNA sequencing reveals cell heterogeneity and transcriptome profile of breast cancer lymph node metastasis. Oncogenesis 10, 66 (2021).

doi: 10.1038/s41389-021-00355-6 pubmed: 34611125 pmcid: 8492772

Kumegawa, K. et al. GRHL2 motif is associated with intratumor heterogeneity of cis-regulatory elements in luminal breast cancer. npj Breast Cancer 8, 70 (2022).

doi: 10.1038/s41523-022-00438-6 pubmed: 35676392 pmcid: 9177858

Kim, H. et al. Single-cell transcriptional and epigenetic profiles of male breast cancer nominate salient cancer-specific enhancers. Int. J. Mol. Sci. 24, 13053 (2023).

doi: 10.3390/ijms241713053 pubmed: 37685859 pmcid: 10487538

Mei, Y. et al. Single-cell analyses reveal suppressive tumor microenvironment of human colorectal cancer. Clin. Transl. Med. 11, e422 (2021).

doi: 10.1002/ctm2.422 pubmed: 34185431 pmcid: 8181206

Li, S. et al. Chromatin accessibility dynamics in colorectal cancer liver metastasis: uncovering the liver tropism at single cell resolution. Pharmacol. Res. 195, 106896 (2023).

doi: 10.1016/j.phrs.2023.106896 pubmed: 37633511

Sun, X. et al. Single-cell analyses reveal cannabidiol rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with anti-PD-1 in colon cancer. J. Pharm. Anal. 13, 726–744 (2023).

doi: 10.1016/j.jpha.2023.04.013 pubmed: 37577382 pmcid: 10422166

Liu, Z. et al. Single-cell chromatin accessibility analysis reveals the epigenetic basis and signature transcription factors for the molecular subtypes of colorectal cancers. Cancer Discov. 14, 1082–1105 (2024).

doi: 10.1158/2159-8290.CD-23-1445 pubmed: 38445965

Babikir, H. et al. ATRX regulates glial identity and the tumor microenvironment in IDH-mutant glioma. Genome Biol. 22, 311 (2021).

doi: 10.1186/s13059-021-02535-4 pubmed: 34763709 pmcid: 8588616

Nikolic, A. et al. Copy-scAT: deconvoluting single-cell chromatin accessibility of genetic subclones in cancer. Sci. Adv. 7, eabg6045 (2021).

doi: 10.1126/sciadv.abg6045 pubmed: 34644115 pmcid: 8514091

Frede, J. et al. Dynamic transcriptional reprogramming leads to immunotherapeutic vulnerabilities in myeloma. Nat. Cell Biol. 23, 1199–1211 (2021).

doi: 10.1038/s41556-021-00766-y pubmed: 34675390 pmcid: 8764878

Leblay, N. et al. Integrated epigenetic and transcriptional single-cell analysis of t(11;14) multiple myeloma and its BCL2 dependency. Blood 143, 42–56 (2024).

doi: 10.1182/blood.2023020276 pubmed: 37729611

Poos, A. M. et al. Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis. Blood 142, 1633–1646 (2023).

doi: 10.1182/blood.2023019758 pubmed: 37390336 pmcid: 10733835

John, L. et al. Resolving the spatial architecture of myeloma and its microenvironment at the single-cell level. Nat. Commun. 14, 5011 (2023).

doi: 10.1038/s41467-023-40584-4 pubmed: 37591845 pmcid: 10435504

Yamagishi, M. et al. Mechanisms of action and resistance in histone methylation-targeted therapy. Nature 627, 221–228 (2024).

doi: 10.1038/s41586-024-07103-x pubmed: 38383791 pmcid: 10917674

Liu, L. et al. Deconvolution of single-cell multi-omics layers reveals regulatory heterogeneity. Nat. Commun. 10, 470 (2019).

doi: 10.1038/s41467-018-08205-7 pubmed: 30692544 pmcid: 6349937

Anadon, C. M. et al. Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells. Cancer Cell 40, 545–557.e13 (2022).

doi: 10.1016/j.ccell.2022.03.008 pubmed: 35427494 pmcid: 9096229

Foster, D. S. et al. Multiomic analysis reveals conservation of cancer associated fibroblast phenotypes across species and tissue of origin. Cancer Cell 40, 1392–1406.e7 (2022).

doi: 10.1016/j.ccell.2022.09.015 pubmed: 36270275 pmcid: 9669239

Liu, N. Q. et al. SMARCB1 loss activates patient-specific distal oncogenic enhancers in malignant rhabdoid tumors. Nat. Commun. 14, 7762 (2023).

doi: 10.1038/s41467-023-43498-3 pubmed: 38040699 pmcid: 10692191

Raviram, R. et al. Integrated analysis of single-cell chromatin state and transcriptome identified common vulnerability despite glioblastoma heterogeneity. Proc. Natl Acad. Sci. USA 120, e2210991120 (2023).

doi: 10.1073/pnas.2210991120 pubmed: 37155843 pmcid: 10194019

Turkalj, S. et al. GTAC enables parallel genotyping of multiple genomic loci with chromatin accessibility profiling in single cells. Cell Stem Cell 30, 722–740.e11 (2023).

doi: 10.1016/j.stem.2023.04.012 pubmed: 37146586

Lambo, S. et al. A longitudinal single-cell atlas of treatment response in pediatric AML. Cancer Cell 41, 2117–2135.e12 (2023).

doi: 10.1016/j.ccell.2023.10.008 pubmed: 37977148

Kundaje, A. et al. Integrative analysis of 111 reference human epigenomes. Nature 518, 317–330 (2015).

doi: 10.1038/nature14248 pubmed: 25693563 pmcid: 4530010

Rotem, A. et al. Single-cell ChIP–seq reveals cell subpopulations defined by chromatin state. Nat. Biotechnol. 33, 1165–1172 (2015).

doi: 10.1038/nbt.3383 pubmed: 26458175 pmcid: 4636926

Bartosovic, M., Kabbe, M. & Castelo-Branco, G. Single-cell CUT&Tag profiles histone modifications and transcription factors in complex tissues. Nat. Biotechnol. 39, 825–835 (2021). This paper introduces single-cell histone modification profiling to the cancer community with a user-friendly adaptation of scCUT&Tag to 10X technology.

doi: 10.1038/s41587-021-00869-9 pubmed: 33846645 pmcid: 7611252

Lim, J. et al. Transitioning single-cell genomics into the clinic. Nat. Rev. Genet. 24, 573–584 (2023).

doi: 10.1038/s41576-023-00613-w pubmed: 37258725

Slyper, M. et al. A single-cell and single-nucleus RNA-seq toolbox for fresh and frozen human tumors. Nat. Med. 26, 792–802 (2020).

doi: 10.1038/s41591-020-0844-1 pubmed: 32405060 pmcid: 7220853

Zou, D.-D. et al. Single-cell sequencing highlights heterogeneity and malignant progression in actinic keratosis and cutaneous squamous cell carcinoma. eLife 12, e85270 (2023).

doi: 10.7554/eLife.85270 pubmed: 38099574 pmcid: 10783873

Epigenomic heterogeneity as a source of tumour evolution.

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Marthe Laisné (M)

Mathieu Lupien (M)

Céline Vallot (C)

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