A neurodevelopmental epigenetic programme mediated by SMARCD3-DAB1-Reelin signalling is hijacked to promote medulloblastoma metastasis.

Humans Extracellular Matrix Proteins / genetics Medulloblastoma / genetics Phosphorylation Epigenomics Serine Endopeptidases / genetics Cell Adhesion Molecules, Neuronal / genetics Cerebellar Neoplasms / genetics Epigenesis, Genetic Nerve Tissue Proteins / genetics Adaptor Proteins, Signal Transducing / genetics

Journal

Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575

Informations de publication

Date de publication:
03 2023
Historique:
received: 17 01 2022
accepted: 17 01 2023
pubmed: 28 2 2023
medline: 17 3 2023
entrez: 27 2 2023
Statut: ppublish

Résumé

How abnormal neurodevelopment relates to the tumour aggressiveness of medulloblastoma (MB), the most common type of embryonal tumour, remains elusive. Here we uncover a neurodevelopmental epigenomic programme that is hijacked to induce MB metastatic dissemination. Unsupervised analyses of integrated publicly available datasets with our newly generated data reveal that SMARCD3 (also known as BAF60C) regulates Disabled 1 (DAB1)-mediated Reelin signalling in Purkinje cell migration and MB metastasis by orchestrating cis-regulatory elements at the DAB1 locus. We further identify that a core set of transcription factors, enhancer of zeste homologue 2 (EZH2) and nuclear factor I X (NFIX), coordinates with the cis-regulatory elements at the SMARCD3 locus to form a chromatin hub to control SMARCD3 expression in the developing cerebellum and in metastatic MB. Increased SMARCD3 expression activates Reelin-DAB1-mediated Src kinase signalling, which results in a MB response to Src inhibition. These data deepen our understanding of how neurodevelopmental programming influences disease progression and provide a potential therapeutic option for patients with MB.

Identifiants

DOI: 10.1038/s41556-023-01093-0 PMID: 36849558 PMC: PMC10014585
pubmed: 36849558
doi: 10.1038/s41556-023-01093-0
pii: 10.1038/s41556-023-01093-0
pmc: PMC10014585
doi:

Substances chimiques

Extracellular Matrix Proteins 0
Serine Endopeptidases EC 3.4.21.-
Cell Adhesion Molecules, Neuronal 0
DAB1 protein, human 0
Nerve Tissue Proteins 0
Adaptor Proteins, Signal Transducing 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

493-507

Subventions

Organisme : NINDS NIH HHS
ID : R21 NS125218
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM133732
Pays : United States

Informations de copyright

© 2023. The Author(s).

Références

Louis, D. N. et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 131, 803–820 (2016).
Zou, H., Poore, B., Broniscer, A., Pollack, I. F. & Hu, B. Molecular heterogeneity and cellular diversity: implications for precision treatment in medulloblastoma. Cancers https://doi.org/10.3390/cancers12030643 (2020).
Taylor, M. D. et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 123, 465–472 (2012).
pubmed: 22134537 doi: 10.1007/s00401-011-0922-z
Cavalli, F. M. G. et al. Intertumoral heterogeneity within medulloblastoma subgroups. Cancer Cell 31, 737–754.e6 (2017).
pubmed: 28609654 pmcid: 6163053 doi: 10.1016/j.ccell.2017.05.005
Northcott, P. A. et al. Medulloblastomics: the end of the beginning. Nat. Rev. Cancer 12, 818–834 (2012).
pubmed: 23175120 pmcid: 3889646 doi: 10.1038/nrc3410
Garzia, L. et al. A hematogenous route for medulloblastoma leptomeningeal metastases. Cell 172, 1050 (2018); erratum 173, 1549 (2018).
Ramaswamy, V. et al. Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis. Lancet Oncol. 14, 1200–1207 (2013).
pubmed: 24140199 pmcid: 3953419 doi: 10.1016/S1470-2045(13)70449-2
Fults, D. W., Taylor, M. D. & Garzia, L. Leptomeningeal dissemination: a sinister pattern of medulloblastoma growth. J. Neurosurg. Pediatr. https://doi.org/10.3171/2018.11.PEDS18506 (2019).
Chang, C. H., Housepian, E. M. & Herbert, C. Jr. An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas. Radiology 93, 1351–1359 (1969).
pubmed: 4983156 doi: 10.1148/93.6.1351
Vladoiu, M. C. et al. Childhood cerebellar tumours mirror conserved fetal transcriptional programs. Nature 572, 67–73 (2019).
pubmed: 31043743 pmcid: 6675628 doi: 10.1038/s41586-019-1158-7
White, J. J. & Sillitoe, R. V. Development of the cerebellum: from gene expression patterns to circuit maps. Wiley Interdiscip. Rev. Dev. Biol. 2, 149–164 (2013).
pubmed: 23799634 doi: 10.1002/wdev.65
Butts, T., Green, M. J. & Wingate, R. J. Development of the cerebellum: simple steps to make a ‘little brain’. Development 141, 4031–4041 (2014).
pubmed: 25336734 doi: 10.1242/dev.106559
Sathyanesan, A. et al. Emerging connections between cerebellar development, behaviour and complex brain disorders. Nat. Rev. Neurosci. 20, 298–313 (2019).
pubmed: 30923348 pmcid: 7236620 doi: 10.1038/s41583-019-0152-2
Roussel, M. F. & Stripay, J. L. Epigenetic drivers in pediatric medulloblastoma. Cerebellum 17, 28–36 (2018).
pubmed: 29178021 doi: 10.1007/s12311-017-0899-9
Weishaupt, H. et al. Batch-normalization of cerebellar and medulloblastoma gene expression datasets utilizing empirically defined negative control genes. Bioinformatics 35, 3357–3364 (2019).
pubmed: 30715209 pmcid: 6748729 doi: 10.1093/bioinformatics/btz066
Medvedeva, Y. A. et al. EpiFactors: a comprehensive database of human epigenetic factors and complexes. Database 2015, bav067 (2015).
Northcott, P. A. et al. The whole-genome landscape of medulloblastoma subtypes. Nature 547, 311–317 (2017).
pubmed: 28726821 pmcid: 5905700 doi: 10.1038/nature22973
Hovestadt, V. et al. Resolving medulloblastoma cellular architecture by single-cell genomics. Nature 572, 74–79 (2019).
pubmed: 31341285 pmcid: 6754173 doi: 10.1038/s41586-019-1434-6
Archer, T. C. et al. Proteomics, post-translational modifications, and integrative analyses reveal molecular heterogeneity within medulloblastoma subgroups. Cancer Cell 34, 396–410.e8 (2018).
pubmed: 30205044 pmcid: 6372116 doi: 10.1016/j.ccell.2018.08.004
Ivanov, D. P., Coyle, B., Walker, D. A. & Grabowska, A. M. In vitro models of medulloblastoma: choosing the right tool for the job. J. Biotechnol. 236, 10–25 (2016).
pubmed: 27498314 doi: 10.1016/j.jbiotec.2016.07.028
Venet, D., Dumont, J. E. & Detours, V. Most random gene expression signatures are significantly associated with breast cancer outcome. PLoS Comput. Biol. 7, e1002240 (2011).
pubmed: 22028643 pmcid: 3197658 doi: 10.1371/journal.pcbi.1002240
Hanaford, A. R. et al. DiSCoVERing innovative therapies for rare tumors: combining genetically accurate disease models with in silico analysis to identify novel therapeutic targets. Clin. Cancer Res. 22, 3903–3914 (2016).
pubmed: 27012813 pmcid: 5055054 doi: 10.1158/1078-0432.CCR-15-3011
Tissir, F. & Goffinet, A. M. Reelin and brain development. Nat. Rev. Neurosci. 4, 496–505 (2003).
pubmed: 12778121 doi: 10.1038/nrn1113
Keshvara, L., Benhayon, D., Magdaleno, S. & Curran, T. Identification of Reelin-induced sites of tyrosyl phosphorylation on Disabled 1. J. Biol. Chem. 276, 16008–16014 (2001).
Breschi, A. et al. Gene-specific patterns of expression variation across organs and species. Genome Biol. 17, 151 (2016).
pubmed: 27391956 pmcid: 4937605 doi: 10.1186/s13059-016-1008-y
Carter, R. A. et al. A single-cell transcriptional atlas of the developing murine cerebellum. Curr. Biol. 28, 2910–2920.e2 (2018).
pubmed: 30220501 doi: 10.1016/j.cub.2018.07.062
Leto, K., Carletti, B., Williams, I. M., Magrassi, L. & Rossi, F. Different types of cerebellar GABAergic interneurons originate from a common pool of multipotent progenitor cells. J. Neurosci. 26, 11682–11694 (2006).
pubmed: 17093090 pmcid: 6674781 doi: 10.1523/JNEUROSCI.3656-06.2006
Rakic, P. & Sidman, R. L. Histogenesis of cortical layers in human cerebellum, particularly the lamina dissecans. J. Comp. Neurol. 139, 473–500 (1970).
pubmed: 4195699 doi: 10.1002/cne.901390407
Miyata, T. et al. Migration, early axonogenesis, and Reelin-dependent layer-forming behavior of early/posterior-born Purkinje cells in the developing mouse lateral cerebellum. Neural Dev. 5, 23 (2010).
pubmed: 20809939 pmcid: 2942860 doi: 10.1186/1749-8104-5-23
Muller, F. & O’Rahilly, R. The human brain at stages 18–20, including the choroid plexuses and the amygdaloid and septal nuclei. Anat. Embryol. 182, 285–306 (1990).
D’Arcangelo, G. et al. A protein related to extracellular matrix proteins deleted in the mouse mutant reeler. Nature 374, 719–723 (1995).
pubmed: 7715726 doi: 10.1038/374719a0
Rahimi-Balaei, M., Bergen, H., Kong, J. & Marzban, H. Neuronal migration during development of the cerebellum. Front. Cell Neurosci. 12, 484 (2018).
pubmed: 30618631 pmcid: 6304365 doi: 10.3389/fncel.2018.00484
Aldinger, K. A. et al. Spatial and cell type transcriptional landscape of human cerebellar development. Nat Neurosci. https://doi.org/10.1038/s41593-021-00872-y (2021).
Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y. & Greenleaf, W. J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213–1218 (2013).
pubmed: 24097267 pmcid: 3959825 doi: 10.1038/nmeth.2688
Goodman, J. V. et al. The chromatin remodeling enzyme Chd4 regulates genome architecture in the mouse brain. Nat. Commun. 11, 3419 (2020).
pubmed: 32647123 pmcid: 7347877 doi: 10.1038/s41467-020-17065-z
Skene, P. J. & Henikoff, S. An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites. eLife https://doi.org/10.7554/eLife.21856 (2017).
Hainer, S. J. & Fazzio, T. G. High-resolution chromatin profiling using CUT&RUN. Curr. Protoc. Mol. Biol. 126, e85 (2019).
pubmed: 30688406 pmcid: 6422702 doi: 10.1002/cpmb.85
Boulay, G. et al. OTX2 activity at distal regulatory elements shapes the chromatin landscape of group 3 medulloblastoma. Cancer Discov. 7, 288–301 (2017).
pubmed: 28213356 pmcid: 5340587 doi: 10.1158/2159-8290.CD-16-0844
ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012).
doi: 10.1038/nature11247
Lin, C. Y. et al. Active medulloblastoma enhancers reveal subgroup-specific cellular origins. Nature 530, 57–62 (2016).
pubmed: 26814967 pmcid: 5168934 doi: 10.1038/nature16546
Domcke, S. et al. A human cell atlas of fetal chromatin accessibility. Science https://doi.org/10.1126/science.aba7612 (2020).
Pliner, H. A. et al. Cicero predicts cis-regulatory DNA interactions from single-cell chromatin accessibility data. Mol. Cell 71, 858–871.e8 (2018).
pubmed: 30078726 pmcid: 6582963 doi: 10.1016/j.molcel.2018.06.044
Lambert, S. A. et al. The human transcription factors. Cell 175, 598–599 (2018).
pubmed: 30290144 doi: 10.1016/j.cell.2018.09.045
Bock, H. H. & Herz, J. Reelin activates SRC family tyrosine kinases in neurons. Curr. Biol. 13, 18–26 (2003).
pubmed: 12526740 doi: 10.1016/S0960-9822(02)01403-3
Kuo, G., Arnaud, L., Kronstad-O’Brien, P. & Cooper, J. A. Absence of Fyn and Src causes a reeler-like phenotype. J. Neurosci. 25, 8578–8586 (2005).
pubmed: 16162939 pmcid: 6725670 doi: 10.1523/JNEUROSCI.1656-05.2005
Sun, X. et al. Cardiac-enriched BAF chromatin-remodeling complex subunit Baf60c regulates gene expression programs essential for heart development and function. Biol. Open https://doi.org/10.1242/bio.029512 (2018).
Lickert, H. et al. Baf60c is essential for function of BAF chromatin remodelling complexes in heart development. Nature 432, 107–112 (2004).
pubmed: 15525990 doi: 10.1038/nature03071
Jordan, N. V. et al. SWI/SNF chromatin-remodeling factor Smarcd3/Baf60c controls epithelial-mesenchymal transition by inducing Wnt5a signaling. Mol. Cell. Biol. 33, 3011–3025 (2013).
pubmed: 23716599 pmcid: 3719671 doi: 10.1128/MCB.01443-12
Hu, B. et al. Epigenetic activation of WNT5A drives glioblastoma stem cell differentiation and invasive growth. Cell 167, 1281–1295.e18 (2016).
pubmed: 27863244 pmcid: 5320931 doi: 10.1016/j.cell.2016.10.039
Larouche, M. & Hawkes, R. From clusters to stripes: the developmental origins of adult cerebellar compartmentation. Cerebellum 5, 77–88 (2006).
pubmed: 16818382 doi: 10.1080/14734220600804668
Huq, S. et al. Preclinical efficacy of ribavirin in SHH and group 3 medulloblastoma. J. Neurosurg. Pediatr. https://doi.org/10.3171/2020.8.PEDS20561 (2021).
Zhang, H. et al. EZH2 targeting reduces medulloblastoma growth through epigenetic reactivation of the BAI1/p53 tumor suppressor pathway. Oncogene 39, 1041–1048 (2020).
pubmed: 31582835 doi: 10.1038/s41388-019-1036-7
Natsumeda, M. et al. Inhibition of enhancer of zest homologue 2 is a potential therapeutic target for high-MYC medulloblastoma. Neuropathology 39, 71–77 (2019).
pubmed: 30632221 pmcid: 8772614 doi: 10.1111/neup.12534
Alimova, I. et al. Targeting the enhancer of zeste homologue 2 in medulloblastoma. Int. J. Cancer 131, 1800–1809 (2012).
pubmed: 22287205 pmcid: 3375399 doi: 10.1002/ijc.27455
Vo, B. T. et al. Inactivation of Ezh2 upregulates Gfi1 and drives aggressive Myc-driven group 3 medulloblastoma. Cell Rep. 18, 2907–2917 (2017).
pubmed: 28329683 pmcid: 5415387 doi: 10.1016/j.celrep.2017.02.073
Smits, M. et al. EZH2-regulated DAB2IP is a medulloblastoma tumor suppressor and a positive marker for survival. Clin. Cancer Res. 18, 4048–4058 (2012).
pubmed: 22696229 doi: 10.1158/1078-0432.CCR-12-0399
Xu, H. et al. Integrative analysis reveals the transcriptional collaboration between EZH2 and E2F1 in the regulation of cancer-related gene expression. Mol. Cancer Res. 14, 163–172 (2016).
pubmed: 26659825 doi: 10.1158/1541-7786.MCR-15-0313
Xu, K. et al. EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent. Science 338, 1465–1469 (2012).
pubmed: 23239736 pmcid: 3625962 doi: 10.1126/science.1227604
Lee, S. T. et al. Context-specific regulation of NF-κB target gene expression by EZH2 in breast cancers. Mol. Cell 43, 798–810 (2011).
pubmed: 21884980 doi: 10.1016/j.molcel.2011.08.011
Fraser, J. et al. Granule neuron precursor cell proliferation is regulated by NFIX and intersectin 1 during postnatal cerebellar development. Brain Struct. Funct. 224, 811–827 (2019).
pubmed: 30511336 doi: 10.1007/s00429-018-1801-3
Piper, M. et al. NFIB-mediated repression of the epigenetic factor Ezh2 regulates cortical development. J. Neurosci. 34, 2921–2930 (2014).
pubmed: 24553933 pmcid: 3931505 doi: 10.1523/JNEUROSCI.2319-13.2014
Aplenc, R. et al. Pediatric phase I trial and pharmacokinetic study of dasatinib: a report from the children’s oncology group phase I consortium. J. Clin. Oncol. 29, 839–844 (2011).
pubmed: 21263099 pmcid: 3068059 doi: 10.1200/JCO.2010.30.7231
Broniscer, A. et al. Phase 1 trial, pharmacokinetics, and pharmacodynamics of dasatinib combined with crizotinib in children with recurrent or progressive high-grade and diffuse intrinsic pontine glioma. Pediatr. Blood Cancer 65, e27035 (2018).
pubmed: 29512900 pmcid: 5980705 doi: 10.1002/pbc.27035
Galanis, E. et al. A phase 1 and randomized, placebo-controlled phase 2 trial of bevacizumab plus dasatinib in patients with recurrent glioblastoma: Alliance/North Central Cancer Treatment Group N0872. Cancer 125, 3790–3800 (2019).
pubmed: 31290996 doi: 10.1002/cncr.32340
Lu-Emerson, C. et al. Retrospective study of dasatinib for recurrent glioblastoma after bevacizumab failure. J. Neurooncol. 104, 287–291 (2011).
pubmed: 21153679 doi: 10.1007/s11060-010-0489-x
Reardon, D. A. et al. Phase 1 trial of dasatinib plus erlotinib in adults with recurrent malignant glioma. J. Neurooncol. 108, 499–506 (2012).
pubmed: 22407177 pmcid: 3690584 doi: 10.1007/s11060-012-0848-x
Patty, B. J. & Hainer, S. J. Transcription factor chromatin profiling genome-wide using uliCUT&RUN in single cells and individual blastocysts. Nat. Protoc. 16, 2633–2666 (2021).
pubmed: 33911257 pmcid: 8177051 doi: 10.1038/s41596-021-00516-2
Chen, A. et al. Chitinase-3-like-1 protein complexes modulate macrophage-mediated immune suppression in glioblastoma. J. Clin. Invest. https://doi.org/10.1172/JCI147552 (2021).
Goldman, M. J. et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat. Biotechnol. 38, 675–678 (2020).
pubmed: 32444850 pmcid: 7386072 doi: 10.1038/s41587-020-0546-8

Auteurs

Han Zou (H)

Xiangya School of Medicine, Central South University, Changsha, China.
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Changsha, China.
Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
John G. Rangos Sr Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
ORCID: 0000-0002-3574-3379

Bradley Poore (B)

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
John G. Rangos Sr Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Emily E Brown (EE)

Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.

Jieqi Qian (J)

John G. Rangos Sr Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Bin Xie (B)

Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.

Evridiki Asimakidou (E)

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
John G. Rangos Sr Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Vladislav Razskazovskiy (V)

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
John G. Rangos Sr Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Deanna Ayrapetian (D)

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
John G. Rangos Sr Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Vaibhav Sharma (V)

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
John G. Rangos Sr Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Shunjin Xia (S)

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.

Fei Liu (F)

Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.

Apeng Chen (A)

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
John G. Rangos Sr Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Yongchang Guan (Y)

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
John G. Rangos Sr Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Zhengwei Li (Z)

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
John G. Rangos Sr Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Siyi Wanggou (S)

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.

Olivier Saulnier (O)

Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
ORCID: 0000-0003-4111-1017

Michelle Ly (M)

Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.

Wendy Fellows-Mayle (W)

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

Guifa Xi (G)

Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children's Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
ORCID: 0000-0001-9080-3277

Tadanori Tomita (T)

Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children's Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Adam C Resnick (AC)

Center for Data-Driven Discovery in Biomedicine, Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Stephen C Mack (SC)

Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN, USA.
ORCID: 0000-0001-9620-4742

Eric H Raabe (EH)

Division of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Charles G Eberhart (CG)

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Dandan Sun (D)

Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Beth E Stronach (BE)

Office of Research, University of Pittsburgh Health Sciences, Pittsburgh, PA, USA.
ORCID: 0000-0002-1699-8683

Sameer Agnihotri (S)

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
John G. Rangos Sr Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
UPMC Hillman Cancer Center, Pittsburgh, PA, USA.

Gary Kohanbash (G)

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
John G. Rangos Sr Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
UPMC Hillman Cancer Center, Pittsburgh, PA, USA.

Songjian Lu (S)

Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA.

Karl Herrup (K)

Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Jeremy N Rich (JN)

Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
UPMC Hillman Cancer Center, Pittsburgh, PA, USA.

George K Gittes (GK)

John G. Rangos Sr Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Alberto Broniscer (A)

John G. Rangos Sr Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Zhongliang Hu (Z)

Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.

Xuejun Li (X)

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
Hunan International Scientific and Technological Cooperation Base of Brain Tumor Research, Changsha, China.

Ian F Pollack (IF)

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
John G. Rangos Sr Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
UPMC Hillman Cancer Center, Pittsburgh, PA, USA.

Robert M Friedlander (RM)

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
ORCID: 0000-0002-5008-7592

Sarah J Hainer (SJ)

Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA. sarah.hainer@pitt.edu.
UPMC Hillman Cancer Center, Pittsburgh, PA, USA. sarah.hainer@pitt.edu.
ORCID: 0000-0003-0503-1183

Michael D Taylor (MD)

Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada. mdt.cns@gmail.com.
ORCID: 0000-0001-7009-3466

Baoli Hu (B)

Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA. baolihu@pitt.edu.
John G. Rangos Sr Research Center, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA. baolihu@pitt.edu.
UPMC Hillman Cancer Center, Pittsburgh, PA, USA. baolihu@pitt.edu.
Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. baolihu@pitt.edu.
ORCID: 0000-0002-2737-6871

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › A neurodevelopmental epigenetic programme...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › A neurodevelopmental epigenetic programme...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Tumeurs neuroectodermiques primitives › Médulloblastome › A neurodevelopmental epigenetic programme...
questionsmedicales.fr › Métabolisme › Phosphorylation › A neurodevelopmental epigenetic programme...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › Épigénomique › A neurodevelopmental epigenetic programme...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Protéases à sérine › Serine endopeptidases › A neurodevelopmental epigenetic programme...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes de surface › Molécules d'adhérence cellulaire › Molécules d'adhérence cellulaire neuronale › A neurodevelopmental epigenetic programme...
questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › Tumeurs sous-tentorielles › Tumeurs du cervelet › A neurodevelopmental epigenetic programme...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › A neurodevelopmental epigenetic programme...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › A neurodevelopmental epigenetic programme...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › A neurodevelopmental epigenetic programme...