Temporal single-cell atlas of non-neuronal retinal cells reveals dynamic, coordinated multicellular responses to central nervous system injury.
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
received:
14
06
2022
accepted:
13
01
2023
medline:
3
4
2023
pubmed:
23
2
2023
entrez:
22
2
2023
Statut:
ppublish
Résumé
Non-neuronal cells are key to the complex cellular interplay that follows central nervous system insult. To understand this interplay, we generated a single-cell atlas of immune, glial and retinal pigment epithelial cells from adult mouse retina before and at multiple time points after axonal transection. We identified rare subsets in naive retina, including interferon (IFN)-response glia and border-associated macrophages, and delineated injury-induced changes in cell composition, expression programs and interactions. Computational analysis charted a three-phase multicellular inflammatory cascade after injury. In the early phase, retinal macroglia and microglia were reactivated, providing chemotactic signals concurrent with infiltration of CCR2
Identifiants
pubmed: 36807640
doi: 10.1038/s41590-023-01437-w
pii: 10.1038/s41590-023-01437-w
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
700-713Informations de copyright
© 2023. Springer Nature America, Inc.
Références
Gadani, S. P., Walsh, J. T., Lukens, J. R. & Kipnis, J. Dealing with danger in the CNS: the response of the immune system to injury. Neuron 87, 47–62 (2015).
doi: 10.1016/j.neuron.2015.05.019
pubmed: 26139369
pmcid: 4491143
Shechter, R. & Schwartz, M. CNS sterile injury: just another wound healing? Trends Mol. Med. 19, 135–143 (2013).
doi: 10.1016/j.molmed.2012.11.007
pubmed: 23279948
Burda, J. E. & Sofroniew, M. V. Reactive gliosis and the multicellular response to CNS damage and disease. Neuron 81, 229–248 (2014).
doi: 10.1016/j.neuron.2013.12.034
pubmed: 24462092
pmcid: 3984950
Andries, L., De Groef, L. & Moons, L. Neuroinflammation and optic nerve regeneration: where do we stand in elucidating underlying cellular and molecular players? Curr. Eye Res. 45, 397–409 (2020).
doi: 10.1080/02713683.2019.1669664
pubmed: 31567007
Greenhalgh, A. D., David, S. & Bennett, F. C. Immune cell regulation of glia during CNS injury and disease. Nat. Rev. Neurosci. 21, 139–152 (2020).
doi: 10.1038/s41583-020-0263-9
pubmed: 32042145
Williams, P. R., Benowitz, L. I., Goldberg, J. L. & He, Z. Axon regeneration in the mammalian optic nerve. Annu. Rev. Vis. Sci. 6, 195–213 (2020).
doi: 10.1146/annurev-vision-022720-094953
pubmed: 32936739
Tran, N. M. et al. Single-cell profiles of retinal ganglion cells differing in resilience to injury reveal neuroprotective genes. Neuron 104, 1039–1055 (2019).
doi: 10.1016/j.neuron.2019.11.006
pubmed: 31784286
pmcid: 6923571
Bray, E. R. et al. Thrombospondin-1 mediates axon regeneration in retinal ganglion cells. Neuron 103, 642–657 (2019).
doi: 10.1016/j.neuron.2019.05.044
pubmed: 31255486
pmcid: 6706310
Jacobi, A. et al. Overlapping transcriptional programs promote survival and axonal regeneration of injured retinal ganglion cells. Neuron 110, 2625–2645 (2022).
doi: 10.1016/j.neuron.2022.06.002
pubmed: 35767994
Moalem, G. et al. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat. Med. 5, 49–55 (1999).
doi: 10.1038/4734
pubmed: 9883839
Sas, A. R. et al. A new neutrophil subset promotes CNS neuron survival and axon regeneration. Nat. Immunol. 21, 1496–1505 (2020).
doi: 10.1038/s41590-020-00813-0
pubmed: 33106668
pmcid: 7677206
Kurimoto, T. et al. Neutrophils express oncomodulin and promote optic nerve regeneration. J. Neurosci. 33, 14816–14824 (2013).
doi: 10.1523/JNEUROSCI.5511-12.2013
pubmed: 24027282
pmcid: 3771038
Guttenplan, K. A. et al. Neurotoxic reactive astrocytes drive neuronal death after retinal injury. Cell Rep. 31, 107776 (2020).
doi: 10.1016/j.celrep.2020.107776
pubmed: 32579912
pmcid: 8091906
London, A. et al. Neuroprotection and progenitor cell renewal in the injured adult murine retina requires healing monocyte-derived macrophages. J. Exp. Med 208, 23–39 (2011).
doi: 10.1084/jem.20101202
pubmed: 21220455
pmcid: 3023128
Benhar, I., Reemst, K., Kalchenko, V. & Schwartz, M. The retinal pigment epithelium as a gateway for monocyte trafficking into the eye. EMBO J. 35, 1219–1235 (2016).
doi: 10.15252/embj.201694202
pubmed: 27107049
pmcid: 4888238
O'Koren, E. G. et al. Microglial function is distinct in different anatomical locations during retinal homeostasis and degeneration. Immunity 50, 723–737 (2019).
doi: 10.1016/j.immuni.2019.02.007
pubmed: 30850344
pmcid: 6592635
McMenamin, P. G., Saban, D. R. & Dando, S. J. Immune cells in the retina and choroid: two different tissue environments that require different defenses and surveillance. Prog. Retin. Eye Res. 70, 85–98 (2019).
doi: 10.1016/j.preteyeres.2018.12.002
pubmed: 30552975
Geisert, E. E. et al. Gene expression in the mouse eye: an online resource for genetics using 103 strains of mice. Mol. Vis. 15, 1730–1763 (2009).
pubmed: 19727342
pmcid: 2736153
Youkilis, J. C. & Bassnett, S. Single-cell RNA-sequencing analysis of the ciliary epithelium and contiguous tissues in the mouse eye. Exp. Eye Res. 213, 108811 (2021).
doi: 10.1016/j.exer.2021.108811
pubmed: 34717927
pmcid: 8860325
Lehmann, G. L. et al. Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid. J. Exp. Med. 217, e20190730 (2020).
doi: 10.1084/jem.20190730
pubmed: 32196081
pmcid: 7971135
Korin, B. et al. High-dimensional, single-cell characterization of the brain’s immune compartment. Nat. Neurosci. 20, 1300–1309 (2017).
doi: 10.1038/nn.4610
pubmed: 28758994
Mrdjen, D. et al. High-dimensional single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health, aging, and disease. Immunity 48, 380–395 (2018).
doi: 10.1016/j.immuni.2018.01.011
pubmed: 29426702
Van Hove, H. et al. A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment. Nat. Neurosci. 22, 1021–1035 (2019).
doi: 10.1038/s41593-019-0393-4
pubmed: 31061494
Jordão, M. J. C. et al. Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation. Science 363, eaat7554 (2019).
doi: 10.1126/science.aat7554
pubmed: 30679343
Vecino, E., David Rodriguez, F., Ruzafa, N., Pereiro, X. & Sharma, S. C. Glia-neuron interactions in the mammalian retina. Prog. Retin. Eye Res. 51, 1–40 (2016).
doi: 10.1016/j.preteyeres.2015.06.003
pubmed: 26113209
Hammond, T. R. et al. Single-cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes. Immunity 50, 253–271 (2019).
doi: 10.1016/j.immuni.2018.11.004
pubmed: 30471926
Ronning, K. E., Karlen, S. J., Miller, E. B. & Burns, M. E. Molecular profiling of resident and infiltrating mononuclear phagocytes during rapid adult retinal degeneration using single-cell RNA sequencing. Sci. Rep. 9, 4858 (2019).
doi: 10.1038/s41598-019-41141-0
pubmed: 30890724
pmcid: 6425014
Krasemann, S. et al. The TREM2–APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566–581 (2017).
doi: 10.1016/j.immuni.2017.08.008
pubmed: 28930663
pmcid: 5719893
Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290 (2017).
doi: 10.1016/j.cell.2017.05.018
pubmed: 28602351
Wieghofer, P. et al. Mapping the origin and fate of myeloid cells in distinct compartments of the eye by single-cell profiling. EMBO J. 40, e105123 (2021).
doi: 10.15252/embj.2020105123
pubmed: 33555074
pmcid: 7957431
Hoang, T. et al. Gene regulatory networks controlling vertebrate retinal regeneration. Science 370, eabb8598 (2020).
doi: 10.1126/science.abb8598
pubmed: 33004674
pmcid: 7899183
Habib, N. et al. Disease-associated astrocytes in Alzheimer’s disease and aging. Nat. Neurosci. 23, 701–706 (2020).
doi: 10.1038/s41593-020-0624-8
pubmed: 32341542
pmcid: 9262034
Hasel, P., Rose, I. V. L., Sadick, J. S., Kim, R. D. & Liddelow, S. A. Neuroinflammatory astrocyte subtypes in the mouse brain. Nat. Neurosci. 24, 1475–1487 (2021).
doi: 10.1038/s41593-021-00905-6
pubmed: 34413515
Zamanian, J. L. et al. Genomic analysis of reactive astrogliosis. J. Neurosci. 32, 6391–6410 (2012).
doi: 10.1523/JNEUROSCI.6221-11.2012
pubmed: 22553043
pmcid: 3480225
Liddelow, S. A. et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541, 481–487 (2017).
doi: 10.1038/nature21029
pubmed: 28099414
pmcid: 5404890
Qu, J. & Jakobs, T. C. The time course of gene expression during reactive gliosis in the optic nerve. PLoS ONE 8, e67094 (2013).
doi: 10.1371/journal.pone.0067094
pubmed: 23826199
pmcid: 3694957
Wohl, S. G., Schmeer, C. W., Kretz, A., Witte, O. W. & Isenmann, S. Optic nerve lesion increases cell proliferation and nestin expression in the adult mouse eye in vivo. Exp. Neurol. 219, 175–186 (2009).
doi: 10.1016/j.expneurol.2009.05.008
pubmed: 19445936
Babcock, A. A., Kuziel, W. A., Rivest, S. & Owens, T. Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS. J. Neurosci. 23, 7922–7930 (2003).
doi: 10.1523/JNEUROSCI.23-21-07922.2003
pubmed: 12944523
pmcid: 6740601
Bosch, M. et al. Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense. Science 370, eaay8085 (2020).
doi: 10.1126/science.aay8085
pubmed: 33060333
Zahabi, A. et al. A new efficient protocol for directed differentiation of retinal pigmented epithelial cells from normal and retinal disease induced pluripotent stem cells. Stem Cells Dev. 21, 2262–2272 (2012).
doi: 10.1089/scd.2011.0599
pubmed: 22145677
Zhao, C. et al. mTOR-mediated dedifferentiation of the retinal pigment epithelium initiates photoreceptor degeneration in mice. J. Clin. Invest. 121, 369–383 (2011).
doi: 10.1172/JCI44303
pubmed: 21135502
Yang, J.-Y. et al. Retinal protection by sustained nanoparticle delivery of oncostatin M and ciliary neurotrophic factor into rodent models of retinal degeneration. Transl. Vis. Sci. Technol. 10, 6 (2021).
doi: 10.1167/tvst.10.9.6
pubmed: 34347033
pmcid: 8340648
Reinhard, J., Roll, L. & Faissner, A. Tenascins in retinal and optic nerve neurodegeneration. Front. Integr. Neurosci. 11, 30 (2017).
doi: 10.3389/fnint.2017.00030
pubmed: 29109681
pmcid: 5660115
Shemer, A. et al. Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge. Nat. Commun. 9, 5206 (2018).
doi: 10.1038/s41467-018-07548-5
pubmed: 30523248
pmcid: 6284018
Eraslan, G. et al. Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function. Science 376, eabl4290 (2022).
doi: 10.1126/science.abl4290
pubmed: 35549429
pmcid: 9383269
Jaitin, D. A. et al. Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner. Cell 178, 686–698 (2019).
doi: 10.1016/j.cell.2019.05.054
pubmed: 31257031
pmcid: 7068689
Absinta, M. et al. A lymphocyte–microglia–astrocyte axis in chronic active multiple sclerosis. Nature 597, 709–714 (2021).
doi: 10.1038/s41586-021-03892-7
pubmed: 34497421
pmcid: 8719282
Margeta, M. A. et al. Apolipoprotein E4 impairs the response of neurodegenerative retinal microglia and prevents neuronal loss in glaucoma. Immunity 55, 1627–1644 (2022).
doi: 10.1016/j.immuni.2022.07.014
pubmed: 35977543
O’Koren, E. G., Mathew, R. & Saban, D. R. Fate mapping reveals that microglia and recruited monocyte-derived macrophages are definitively distinguishable by phenotype in the retina. Sci. Rep. 6, 20636 (2016).
doi: 10.1038/srep20636
pubmed: 26856416
pmcid: 4746646
Xu, H., Dawson, R., Forrester, J. V. & Liversidge, J. Identification of novel dendritic cell populations in normal mouse retina. Invest. Ophthalmol. Vis. Sci. 48, 1701–1710 (2007).
doi: 10.1167/iovs.06-0697
pubmed: 17389502
Yona, S. et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38, 79–91 (2013).
doi: 10.1016/j.immuni.2012.12.001
pubmed: 23273845
Mathys, H. et al. Temporal tracking of microglia activation in neurodegeneration at single-cell resolution. Cell Rep. 21, 366–380 (2017).
doi: 10.1016/j.celrep.2017.09.039
pubmed: 29020624
pmcid: 5642107
Sala Frigerio, C. et al. The major risk factors for Alzheimer’s disease: age, sex, and genes modulate the microglia response to Aβ plaques. Cell Rep. 27, 1293–1306 (2019).
doi: 10.1016/j.celrep.2019.03.099
pubmed: 31018141
Zhan, L. et al. Proximal recolonization by self-renewing microglia re-establishes microglial homeostasis in the adult mouse brain. PLoS Biol. 17, e3000134 (2019).
doi: 10.1371/journal.pbio.3000134
pubmed: 30735499
pmcid: 6383943
Huang, Y. et al. Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion. Nat. Neurosci. 21, 530–540 (2018).
doi: 10.1038/s41593-018-0090-8
pubmed: 29472620
Rothhammer, V. et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat. Med. 22, 586–597 (2016).
doi: 10.1038/nm.4106
pubmed: 27158906
pmcid: 4899206
Mostafavi, S. et al. Parsing the interferon transcriptional network and its disease associations. Cell 164, 564–578 (2016).
doi: 10.1016/j.cell.2015.12.032
pubmed: 26824662
pmcid: 4743492
Kuse, Y., Tsuruma, K., Mizoguchi, T., Shimazawa, M. & Hara, H. Progranulin deficiency causes the retinal ganglion cell loss during development. Sci. Rep. 7, 1679 (2017).
doi: 10.1038/s41598-017-01933-8
pubmed: 28490764
pmcid: 5431873
Vigneswara, V., Berry, M., Logan, A. & Ahmed, Z. Pigment epithelium-derived factor is retinal ganglion cell neuroprotective and axogenic after optic nerve crush injury. Invest. Ophthalmol. Vis. Sci. 54, 2624–2633 (2013).
doi: 10.1167/iovs.13-11803
pubmed: 23513062
pmcid: 3630817
Jolly, S. et al. G protein-coupled receptor 37-like 1 modulates astrocyte glutamate transporters and neuronal NMDA receptors and is neuroprotective in ischemia. Glia 66, 47–61 (2018).
doi: 10.1002/glia.23198
pubmed: 28795439
Ma, W. et al. Absence of TGFβ signaling in retinal microglia induces retinal degeneration and exacerbates choroidal neovascularization. eLife 8, e42049 (2019).
doi: 10.7554/eLife.42049
pubmed: 30666961
pmcid: 6342522
Fourgeaud, L. et al. TAM receptors regulate multiple features of microglial physiology. Nature 532, 240–244 (2016).
doi: 10.1038/nature17630
pubmed: 27049947
pmcid: 5358512
Sanmarco, L. M. et al. Gut-licensed IFNγ
doi: 10.1038/s41586-020-03116-4
pubmed: 33408417
pmcid: 8039910
Lückoff, A. et al. Interferon‐β signaling in retinal mononuclear phagocytes attenuates pathological neovascularization. EMBO Mol. Med. 8, 670–678 (2016).
doi: 10.15252/emmm.201505994
pubmed: 27137488
pmcid: 4888856
Wang, W. et al. Type I interferon therapy limits CNS autoimmunity by inhibiting CXCR3-mediated trafficking of pathogenic effector T cells. Cell Rep. 28, 486–497 (2019).
doi: 10.1016/j.celrep.2019.06.021
pubmed: 31291583
pmcid: 6748389
Brennan, F. H. et al. Microglia coordinate cellular interactions during spinal cord repair in mice. Nat. Commun. 13, 4096 (2022).
doi: 10.1038/s41467-022-31797-0
pubmed: 35835751
pmcid: 9283484
Roy, E. R. et al. Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease. J. Clin. Invest. 130, 1912–1930 (2020).
doi: 10.1172/JCI133737
pubmed: 31917687
pmcid: 7108898
Chakarov, S. et al. Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches. Science 363, eaau0964 (2019).
doi: 10.1126/science.aau0964
pubmed: 30872492
Kierdorf, K., Masuda, T., Jordão, M. J. C. & Prinz, M. Macrophages at CNS interfaces: ontogeny and function in health and disease. Nat. Rev. Neurosci. 20, 547–562 (2019).
doi: 10.1038/s41583-019-0201-x
pubmed: 31358892
Anderson, S. R. et al. Developmental apoptosis promotes a disease-related gene signature and independence from CSF1R signaling in retinal microglia. Cell Rep. 27, 2002–2013 (2019).
doi: 10.1016/j.celrep.2019.04.062
pubmed: 31091440
pmcid: 6544177
Vong, L. et al. Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron 71, 142–154 (2011).
doi: 10.1016/j.neuron.2011.05.028
pubmed: 21745644
pmcid: 3134797
Buffelli, M. et al. Genetic evidence that relative synaptic efficacy biases the outcome of synaptic competition. Nature 424, 430–434 (2003).
doi: 10.1038/nature01844
pubmed: 12879071
Saederup, N. et al. Selective chemokine receptor usage by central nervous system myeloid cells in CCR2–red fluorescent protein knock-in mice. PLoS ONE 5, e13693 (2010).
doi: 10.1371/journal.pone.0013693
pubmed: 21060874
pmcid: 2965160
Fernandez-Godino, R., Garland, D. L. & Pierce, E. A. Isolation, culture and characterization of primary mouse RPE cells. Nat. Protoc. 11, 1206–1218 (2016).
doi: 10.1038/nprot.2016.065
pubmed: 27281648
Takahama, S. et al. Retinal astrocytes and GABAergic wide-field amacrine cells express PDGFRα: connection to retinal ganglion cell neuroprotection by PDGF-AA. Invest. Ophthalmol. Vis. Sci. 58, 4703–4711 (2017).
doi: 10.1167/iovs.21783
pubmed: 28910446
pmcid: 5606213
Macosko, E. Z. et al. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161, 1202–1214 (2015).
doi: 10.1016/j.cell.2015.05.002
pubmed: 26000488
pmcid: 4481139
Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).
doi: 10.1038/nmeth.2019
pubmed: 22743772
Mack, M. et al. Expression and characterization of the chemokine receptors CCR2 and CCR5 in mice. J. Immunol. 166, 4697–4704 (2001).
doi: 10.4049/jimmunol.166.7.4697
pubmed: 11254730
Okunuki, Y. et al. Retinal microglia initiate neuroinflammation in ocular autoimmunity. Proc. Natl Acad. Sci. USA 116, 9989–9998 (2019).
doi: 10.1073/pnas.1820387116
pubmed: 31023885
pmcid: 6525481
Ding, J. & Regev, A. Deep generative model embedding of single-cell RNA-Seq profiles on hyperspheres and hyperbolic spaces. Nat. Commun. 12, 2554 (2021).
doi: 10.1038/s41467-021-22851-4
pubmed: 33953202
pmcid: 8099904
Blondel, V. D., Guillaume, J.-L., Lambiotte, R. & Lefebvre, E. Fast unfolding of communities in large networks. J. Stat. Mech. 2008, P10008 (2008).
doi: 10.1088/1742-5468/2008/10/P10008
Levine, J. H. et al. Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis. Cell 162, 184–197 (2015).
doi: 10.1016/j.cell.2015.05.047
pubmed: 26095251
pmcid: 4508757
Ding, J. et al. Systematic comparison of single-cell and single-nucleus RNA-sequencing methods. Nat. Biotechnol. 38, 737–746 (2020).
doi: 10.1038/s41587-020-0465-8
pubmed: 32341560
pmcid: 7289686
Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587 (2021).
doi: 10.1016/j.cell.2021.04.048
pubmed: 34062119
pmcid: 8238499
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).
doi: 10.1073/pnas.0506580102
pubmed: 16199517
pmcid: 1239896
Liberzon, A. et al. The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst. 1, 417–425 (2015).
doi: 10.1016/j.cels.2015.12.004
pubmed: 26771021
pmcid: 4707969
Tirosh, I. et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352, 189–196 (2016).
doi: 10.1126/science.aad0501
pubmed: 27124452
pmcid: 4944528
Schiebinger, G. et al. Optimal-transport analysis of single-cell gene expression identifies developmental trajectories in reprogramming. Cell 176, 928–943 (2019).
doi: 10.1016/j.cell.2019.01.006
pubmed: 30712874
pmcid: 6402800
La Manno, G. et al. RNA velocity of single cells. Nature 560, 494–498 (2018).
doi: 10.1038/s41586-018-0414-6
pubmed: 30089906
pmcid: 6130801
Bergen, V., Lange, M., Peidli, S., Wolf, F. A. & Theis, F. J. Generalizing RNA velocity to transient cell states through dynamical modeling. Nat. Biotechnol. 38, 1408–1414 (2020).
doi: 10.1038/s41587-020-0591-3
pubmed: 32747759
Jerby-Arnon, L. & Regev, A. DIALOGUE maps multicellular programs in tissue from single-cell or spatial transcriptomics data. Nat. Biotechnol. 40, 1467–1477 (2022).
doi: 10.1038/s41587-022-01288-0
pubmed: 35513526
pmcid: 9547813
Baccin, C. et al. Combined single-cell and spatial transcriptomics reveal the molecular, cellular and spatial bone marrow niche organization. Nat. Cell Biol. 22, 38–48 (2020).
doi: 10.1038/s41556-019-0439-6
pubmed: 31871321
Hou, R., Denisenko, E., Ong, H. T., Ramilowski, J. A. & Forrest, A. R. R. Predicting cell-to-cell communication networks using NATMI. Nat. Commun. 11, 5011 (2020).
doi: 10.1038/s41467-020-18873-z
pubmed: 33024107
pmcid: 7538930
Wheeler, M. A. et al. MAFG-driven astrocytes promote CNS inflammation. Nature 578, 593–599 (2020).
doi: 10.1038/s41586-020-1999-0
pubmed: 32051591
pmcid: 8049843
Goldberger, J., Hinton, G. E., Roweis, S. & Salakhutdinov, R. R. Neighbourhood components analysis. In Advances in Neural Information Processing Systems 17 (NIPS 2004) (eds Saul, L. et al.) (MIT Press, 2004).
van den Brink, S. C. et al. Single-cell sequencing reveals dissociation-induced gene expression in tissue subpopulations. Nat. Methods 14, 935–936 (2017).
doi: 10.1038/nmeth.4437
pubmed: 28960196
Gharahkhani, P. et al. Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries. Nat. Commun. 12, 1258 (2021).
doi: 10.1038/s41467-020-20851-4
pubmed: 33627673
pmcid: 7904932
Han, X. et al. Automated AI labeling of optic nerve head enables insights into cross-ancestry glaucoma risk and genetic discovery in >280,000 images from UKB and CLSA. Am. J. Hum. Genet. 108, 1204–1216 (2021).
doi: 10.1016/j.ajhg.2021.05.005
pubmed: 34077762
pmcid: 8322932
van Zyl, T. et al. Cell atlas of the human ocular anterior segment: tissue-specific and shared cell types. Proc. Natl Acad. Sci. USA 119, e2200914119 (2022).
doi: 10.1073/pnas.2200914119
pubmed: 35858321
pmcid: 9303934