AbstractThe development of the retina is under tight temporal and spatial control. To gain insights into the molecular basis of this process, we generate a single-nuclei dual-omic atlas of the human developing retina with approximately 220,000 nuclei from 14 human embryos and fetuses aged between 8 and 23-weeks post-conception with matched macular and peripheral tissues.

摘要视网膜的发育受到严格的时空控制。为了深入了解这一过程的分子基础，我们生成了人类发育视网膜的单核双组学图谱，其中来自14个人类胚胎和受孕后8至23周之间的胎儿的约220000个核与匹配的黄斑和外周组织。

This atlas captures all major cell classes in the retina, along with a large proportion of progenitors and cell-type-specific precursors. Cell trajectory analysis reveals a transition from continuous progression in early progenitors to a hierarchical development during the later stages of cell type specification.

。细胞轨迹分析揭示了从早期祖细胞的连续进展到细胞类型规范后期的分层发展的转变。

Both known and unrecorded candidate transcription factors, along with gene regulatory networks that drive the transitions of various cell fates, are identified. Comparisons between the macular and peripheral retinae indicate a largely consistent yet distinct developmental pattern. This atlas offers unparalleled resolution into the transcriptional and chromatin accessibility landscapes during development, providing an invaluable resource for deeper insights into retinal development and associated diseases..

确定了已知和未记录的候选转录因子，以及驱动各种细胞命运转变的基因调控网络。黄斑视网膜和周围视网膜之间的比较表明，其发育模式基本一致但截然不同。该图谱为发育过程中的转录和染色质可及性景观提供了无与伦比的分辨率，为深入了解视网膜发育和相关疾病提供了宝贵的资源。。

IntroductionAs part of the central nervous system, the human retina is a well-organized, multilayered neuronal structure containing seven major cell classes: photoreceptors (cones and rods), amacrine cells (ACs), bipolar cells (BCs), horizontal cells (HCs), retinal ganglion cells (RGCs), and Müller glial cells (MGs)1.

引言作为中枢神经系统的一部分，人类视网膜是一种组织良好的多层神经元结构，包含七种主要细胞类别：光感受器（视锥细胞和视杆细胞），无长突细胞（ACs），双极细胞（BCs），水平细胞（HCs），视网膜神经节细胞（RGCs）和Müller神经胶质细胞（MGs）1。

Furthermore, these cell classes can be divided into approximately 110 distinct cell types2.Guided by a multitude of cell fate determinants, these diverse sets of retinal neurons are derived from a common pool of retinal progenitor cells (RPCs)3 in both sequential and overlapping patterns4,5,6,7,8. First, RPCs divide symmetrically to increase the cell population.

此外，这些细胞类别可分为大约110种不同的细胞类型2。在多种细胞命运决定因素的指导下，这些不同的视网膜神经元来源于视网膜祖细胞（RPCs）3的共同池，顺序和重叠模式4,5,6,7,8。首先，RPC对称分裂以增加细胞群。

They then either divide asymmetrically to produce two daughter cells—one that differentiates and the other that remains a progenitor—or they divide symmetrically into two differentiated daughter cells in later stages7,9,10. RPCs can be divided into two major subtypes: primary RPCs (PRPCs) and neurogenic RPCs (NRPCs).

然后，它们要么不对称分裂产生两个子细胞，一个分化，另一个保留祖细胞，要么在后期对称分裂成两个分化的子细胞7,9,10。RPC可分为两种主要亚型：原发性RPC（PRPC）和神经源性RPC（NRPC）。

PRPCs are typically enriched in cell-cycle associated transcripts, whereas NRPCs are characterized by proneural transcription factors (TFs) that will allow at least one daughter cell to exit the cell cycle and differentiate into a mature retinal neuron11,12.RPCs have heterogeneous transcriptomes and competencies before they are specified and differentiated into a particular cell fate13,14.

。

This dynamic yet organized differentiation process generally happens in two phases: in the first phase, RGCs, ACs, HCs, and cones are produced; and in the second, BCs, rods, and MGs are produced9,15,16. Also, by RLBP1 immunolabeling, the most recent publication showed that MGs develop in the presumptive fovea as early as fetal day 5917, earlier than previously known.In addition to temporal control, t.

这种动态而有组织的分化过程通常发生在两个阶段：在第一阶段，产生RGC，AC，HC和视锥细胞；第二，生产BCs，棒和MGs 9,15,16。此外，通过RLBP1免疫标记，最近的出版物显示MGs早在胎儿第5917天就在假定的中央凹中发育，比以前已知的要早。除了时间控制之外，t。

Data availability

数据可用性

The RNA-seq and ATAC-seq raw data generated in this study can be accessed at National Center for Biotechnology Information (NCBI) with Sequence Read Archive (SRA) accession ID SRP510712. A copy of raw data has been deposited in the HCA Data Portal - Human Cell Atlas, under accession code 581de139-461f-4875-b408-56453a9082c7 [https://explore.data.humancellatlas.org/projects/581de139-461f-4875-b408-56453a9082c7].

。原始数据的副本已保存在HCA数据门户-人类细胞图谱中，登录号为581de139-461f-4875-b408-56453a9082c7[https://explore.data.humancellatlas.org/projects/581de139-461f-4875-b408-56453a9082c7]。

The processed data are available at CZ CELLxGENE Discover with accession code 5900dda8-2dc3-4770-b604084eac1c2c82 [https://cellxgene.cziscience.com/collections/5900dda8-2dc3-4770-b604-084eac1c2c82]. The count matrix for all sequencing data is available at Gene Expression Omnibus, with accession code GSE268630 [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE268630].

处理后的数据可在CZ CELLxGENE Discover上获得，登录号为5900dda8-2dc3-4770-b604084eac1c2c82[https://cellxgene.cziscience.com/collections/5900dda8-2dc3-4770-b604-084eac1c2c82]。所有测序数据的计数矩阵可在Gene Expression Omnibus上获得，登录号为GSE268630[https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE268630]。

The binned ATAC-seq peak signaling data used in this study are available in the UCSC Genome Browser Home under session ID HumanDevelopingRetinaAtlas [https://genome.ucsc.edu/s/zhenzuo2/HumanDevelopingRetinaAtlas]. Adult data used for cell major class annotation and cell subclass annotation is provided in Zenodo [https://doi.org/10.5281/zenodo.10806575].

本研究中使用的分类ATAC-seq峰值信号数据可在UCSC基因组浏览器主页的会话ID HumanDevelopingRetinaAtlas下获得[https://genome.ucsc.edu/s/zhenzuo2/HumanDevelopingRetinaAtlas]。Zenodo中提供了用于细胞主要类注释和细胞子类注释的成人数据[https://doi.org/10.5281/zenodo.10806575]。

Adult differentially accessible regions, adult histone modification regions, inferred gene regulatory network model, recovered dynamic models, identified differentially expressed genes model, and bigwig files for ATAC are provided in Zenodo [https://doi.org/10.5281/zenodo.10866348]. Source data are provided with this paper as a Source Data file. Source data are provided with this paper..

Zenodo中提供了成人差异可及区域，成人组蛋白修饰区域，推断的基因调控网络模型，恢复的动态模型，鉴定的差异表达基因模型以及ATAC的bigwig文件[https://doi.org/10.5281/zenodo.10866348]。本文提供了源数据作为源数据文件。本文提供了源数据。。

Code availability

代码可用性

Analysis scripts can be accessed with GitHub repository https://doi.org/10.5281/zenodo.1125048293.

可以使用GitHub存储库访问分析脚本https://doi.org/10.5281/zenodo.1125048293.

ReferencesLukowski, S. W. et al. A single‐cell transcriptome atlas of the adult human retina. EMBO J. 38, e100811 (2019).Article

参考文献Lukowski，S.W。等人，成人视网膜的单细胞转录组图谱。EMBO J.38，e100811（2019）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Li, J. et al. Integrated multi-omics single cell atlas of the human retina. Preprint at bioRxiv https://doi.org/10.21203/2Frs.3.rs-3471275/2Fv1 (2023).Centanin, L. & Wittbrodt, J. Retinal neurogenesis. Development 141, 241–244 (2014).Article

Li，J。等人。人类视网膜的综合多组学单细胞图谱。bioRxiv预印本https://doi.org/10.21203/2Frs.3.rs-3471275/2Fv1（2023年）。Centanin，L。和Wittbrodt，J。视网膜神经发生。发展141241-244（2014）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Turner, D. L. & Cepko, C. L. A common progenitor for neurons and glia persists in rat retina late in development. Nature 328, 131–136 (1987).Article

Turner，D.L。＆Cepko，C.L。神经元和神经胶质的常见祖细胞在发育后期持续存在于大鼠视网膜中。。文章

ADS

广告

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Holt, C. E., Bertsch, T. W., Ellis, H. M. & Harris, W. A. Cellular determination in the Xenopus retina is independent of lineage and birth date. Neuron 1, 15–26 (1988).Article

Holt，C.E.，Bertsch，T.W.，Ellis，H.M。＆Harris，W.A。非洲爪蟾视网膜中的细胞测定与血统和出生日期无关。神经元1,15-26（1988）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Wetts, R. & Fraser, S. E. Multipotent precursors can give rise to all major cell types of the frog retina. Science 239, 1142–1145 (1988).Article

Wetts，R。＆Fraser，S.E。多能前体可以产生青蛙视网膜的所有主要细胞类型。科学2391142-1145（1988）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Cepko, C. L., Austin, C. P., Yang, X., Alexiades, M. & Ezzeddine, D. Cell fate determination in the vertebrate retina. Proc. Natl Acad. Sci. 93, 589–595 (1996).Article

Cepko，C.L.，Austin，C.P.，Yang，X.，Alexiades，M。＆Ezzeddine，D。脊椎动物视网膜中细胞命运的确定。程序。国家科学院。科学。93589-595（1996）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Davis, D. M. & Dyer, M. A. Retinal progenitor cells, differentiation, and barriers to cell cycle reentry. Curr. Top. Dev. Biol., 93 175–188 (2010).Young, R. W. Cell differentiation in the retina of the mouse. Anat. Rec. 212, 199–205 (1985).Article

Davis，D.M。＆Dyer，M.A。视网膜祖细胞，分化和细胞周期折返障碍。货币。顶部。开发生物学。，93 175–188（2010）。Young，R.W。小鼠视网膜中的细胞分化。阿纳特。记录212199-205（1985）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Dyer, M. A. & Cepko, C. L. Regulating proliferation during retinal development. Nat. Rev. Neurosci. 2, 333–342 (2001).Article

Dyer，M.A。＆Cepko，C.L。在视网膜发育过程中调节增殖。神经科学杂志。2333-342（2001）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Clark, B. S. et al. Single-cell RNA-seq analysis of retinal development identifies NFI factors as regulating mitotic exit and late-born cell specification. Neuron 102, 1111–1126 (2019).Shiau, F., Ruzycki, P. A. & Clark, B. S. A single-cell guide to retinal development: cell fate decisions of multipotent retinal progenitors in scrna-seq.

Clark，B.S.等人。视网膜发育的单细胞RNA-seq分析确定NFI因子调节有丝分裂出口和晚期细胞规格。神经元1021111-1126（2019）。Shiau，F.，Ruzycki，P.A。＆Clark，B.S。视网膜发育的单细胞指南：scrna-seq中多能视网膜祖细胞的细胞命运决定。

Dev. Biol. 478, 41–58 (2021).Article .

开发生物。478,41-58（2021）。文章。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Jensen, A. M. & Raff, M. C. Continuous observation of multipotential retinal progenitor cells in clonal density culture. Dev. Biol. 188, 267–279 (1997).Article

Jensen，A.M。＆Raff，M.C。在克隆密度培养中连续观察多能视网膜祖细胞。开发生物。188267-279（1997）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Alexiades, M. R. & Cepko, C. L. Subsets of retinal progenitors display temporally regulated and distinct biases in the fates of their progeny. Development 124, 1119–1131 (1997).Article

Alexiades，M.R。＆Cepko，C.L。视网膜祖细胞的亚群在其后代的命运中表现出时间调节和明显的偏差。发展1241119-1131（1997）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Prada, C., Puga, J., Perez-Mendez, L., Lopez, R. & Ramirez, G. Spatial and temporal patterns of neurogenesis in the chick retina. Eur. J. Neurosci. 3, 559–569 (1991).Article

Prada，C.，Puga，J.，Perez-Mendez，L.，Lopez，R。＆Ramirez，G。鸡视网膜神经发生的时空模式。Eur.J.Neurosci。3559-569（1991）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Rapaport, D. Spatiotemporal gradients of cell genesis in the primate retina. Perspect. Dev. Neurobiol. 3, 147–159 (1996).CAS

Rapaport，D。灵长类视网膜细胞发生的时空梯度。透视图。神经生物学发展。3147-159（1996）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Wohlschlegel, J. et al. ASCL1 induces neurogenesis in human Muller glia. Stem Cell Rep. 18, 2400–2417 (2023).Article

Wohlschlegel，J。等人。ASCL1诱导人Muller神经胶质细胞的神经发生。干细胞代表182400-2417（2023）。文章

CAS

中科院

Google Scholar

谷歌学者

Tovee, M. J. The molecular genetics and evolution of primate colour vision. Trends Neurosci. 17, 30–37 (1994).Article

Tovee，M.J。灵长类动物色觉的分子遗传学和进化。。17,30-37（1994）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Vorobyev, M. Ecology and evolution of primate colour vision. Clin. Exp. Optom. 87, 230–238 (2004).Article

Vorobyev，M。灵长类动物色觉的生态学和进化。临床。。87230-238（2004）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Provis, J. M., Dubis, A. M., Maddess, T. & Carroll, J. Adaptation of the central retina for high acuity vision: Cones, the fovea and the Avascular Zone. Prog. Retin. Eye Res. 35, 63–81 (2013).Article

。程序。雷丁。Eye Res.35，63–81（2013）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Bringmann, A. et al. The primate fovea: Structure, function and development. Prog. Retin. Eye Res. 66, 49–84 (2018).Article

Bringmann，A。等人。灵长类动物中央凹：结构，功能和发育。程序。雷丁。Eye Res.66,49-84（2018）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Hendrickson, A. E. & Yuodelis, C. The morphological development of the human fovea. Ophthalmology 91, 603–612 (1984).Article

Hendrickson，A.E。和Yuodelis，C。人类中央凹的形态发育。眼科91603-612（1984）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Hendrickson, A., Possin, D., Vajzovic, L. & Toth, C. A. Histologic development of the human fovea from midgestation to maturity. Am. J. Ophthalmol. 154, 767–778 (2012).Article

Hendrickson，A.，Possin，D.，Vajzovic，L。＆Toth，C.A。人类中央凹从妊娠中期到成熟的组织学发育。美国眼科杂志。154767-778（2012）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

O’Brien, K. M. et al. Expression of photoreceptor-specific nuclear receptor NR2E3 in rod photoreceptors of fetal human retina. Investigative Opthalmology amp; Vis. Sci. 45, 2807 (2004).Article

O'Brien，K.M.等人。光感受器特异性核受体NR2E3在胎儿视网膜杆状光感受器中的表达。调查眼科amp；可见。科学。452807（2004）。文章

Google Scholar

谷歌学者

Finlay, B. L., Silveira, L. C. & Reichenbach, A. Comparative aspects of visual system development. The Primate Visual System, 37–72 (2006).da Silva, S. & Cepko, C. L. FGF8 expression and degradation of retinoic acid are required for patterning a high-acuity area in the retina. Dev. Cell 42, 68–81.

Finlay，B.L.，Silveira，L.C。和Reichenbach，A。视觉系统发育的比较方面。灵长类动物视觉系统，37-72（2006）。da Silva，S。和Cepko，C。L。FGF8的表达和视黄酸的降解是形成视网膜高视力区域所必需的。开发单元42、68-81。

(2017).Article .

（2017年）。文章。

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Thomas, E. D. et al. Cell-specific cis-regulatory elements and mechanisms of non-coding genetic disease in human retina and retinal organoids. Dev. Cell 57, 820–836. (2022).Article

Thomas，E.D.等人，《人类视网膜和视网膜类器官中非编码遗传疾病的细胞特异性顺式调控元件和机制》。开发单元57820-836。（2022年）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hoshino, A. et al. Molecular anatomy of the developing human retina. Dev. Cell 43, 763–779.e4 (2017).Article

Hoshino，A.等人，《发育中的人类视网膜的分子解剖学》。Dev.Cell 43763–779.e4（2017）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Li, S. et al. Foxn4 controls the genesis of Amacrine and horizontal cells by retinal progenitors. Neuron 43, 795–807 (2004).Article

。神经元43795-807（2004）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Fish, J. L., Kosodo, Y. & Enard, W. P a abo, S. & Huttner, W. B. Aspm specifically maintains symmetric proliferative divisions of neuroepithelial cells. Proc. Natl Acad. Sci. USA 103, 10438–10443 (2006).Article

Fish，J.L.，Kosodo，Y。＆Enard，W.P a abo，S。＆Huttner，W.B。Aspm特别维持神经上皮细胞的对称增殖分裂。程序。国家科学院。科学。美国10310438–10443（2006）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Trimarchi, J. M., Stadler, M. B. & Cepko, C. L. Individual retinal progenitor cells display extensive heterogeneity of gene expression. PLoS ONE 3, e1588 (2008).Florio, M. et al. Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion. Science 347, 1465–1470 (2015).Article .

Trimarchi，J.M.，Stadler，M.B。＆Cepko，C.L。单个视网膜祖细胞显示出广泛的基因表达异质性。PLoS ONE 3，e1588（2008）。Florio，M。等人。人类特异性基因ARHGAP11B促进基底祖细胞扩增和新皮层扩增。科学3471465-1470（2015）。文章。

ADS

广告

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Fleck, J. S. et al. Inferring and perturbing cell fate regulomes in human brain organoids. Nature (2022).Thompson, C. L. et al. A High-resolution spatiotemporal atlas of gene expression of the developing mouse brain. Neuron 83, 309–323 (2014).Article

Fleck，J.S.等人。推断和扰乱人脑类器官中的细胞命运调节。《自然》（2022）。Thompson，C.L.等人。发育中的小鼠大脑基因表达的高分辨率时空图谱。神经元83309-323（2014）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Sagner, A. et al. A shared transcriptional code orchestrates temporal patterning of the central nervous system. PLOS Biol. 19, e3001450 (2021).Article

Sagner，A。等人。共享的转录代码协调中枢神经系统的时间模式。《公共科学图书馆·生物学》。19，e3001450（2021）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Naef, V. et al. The age-regulated zinc finger factor ZNF367 is a new modulator of neuroblast proliferation during embryonic neurogenesis. Sci. Rep. 8, 11836 (2018).Zhao, M. & Peng, G. Regulatory mechanisms of retinal photoreceptors development at single cell resolution. Int. J. Mol. Sci.

Naef，V。等人。年龄调节的锌指因子ZNF367是胚胎神经发生过程中成神经细胞增殖的新调节剂。科学。代表811836（2018）。Zhao，M。＆Peng，G。单细胞分辨率下视网膜光感受器发育的调节机制。Int.J.Mol.Sci。

22, 8357 (2021).Article .

228357（2021年）。文章。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Dyer, M. A., Livesey, F. J., Cepko, C. L. & Oliver, G. Prox1 function controls progenitor cell proliferation and horizontal cell genesis in the mammalian retina. Nat. Genet. 34, 53–58 (2003).Article

Dyer，M.A.，Livesey，F.J.，Cepko，C.L。和Oliver，G.Prox1功能控制哺乳动物视网膜中的祖细胞增殖和水平细胞发生。纳特·吉内特。34，53-58（2003）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Nishida, A. et al. OTX2 homeobox gene controls retinal photoreceptor cell fate and pineal gland development. Nat. Neurosci. 6, 1255–1263 (2003).Article

Nishida，A。等人。OTX2同源框基因控制视网膜感光细胞的命运和松果体的发育。自然神经科学。61255-1263（2003）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Sato, S. et al. DKK3-Cre Bac transgenic mouse line: A tool for highly efficient gene deletion in retinal progenitor cells. Genesis 45, 502–507 (2007).Article

Sato，S。等人。DKK3-Cre Bac转基因小鼠系：视网膜祖细胞中高效基因缺失的工具。《创世纪》45502-507（2007）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Voinescu, P. E., Kay, J. N. & Sanes, J. R. Birthdays of retinal amacrine cell subtypes are systematically related to their molecular identity and Soma position. J. Comp. Neurol. 517, 737–750 (2009).Article

Voinescu，P.E.，Kay，J.N。＆Sanes，J.R。视网膜无长突细胞亚型的生日与它们的分子身份和体细胞位置系统地相关。J、 公司。神经病学。517737-750（2009）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Fujitani, Y. et al. PTF1A determines horizontal and amacrine cell fates during mouse retinal development. Development 133, 4439–4450 (2006).Article

Fujitani，Y。等人，PTF1A决定了小鼠视网膜发育过程中水平和无长突细胞的命运。发展1334439-4450（2006）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Watanabe, S. et al. Prdm13 Regulates Subtype Specification of Retinal Amacrine Interneurons and Modulates Visual Sensitivity. J. Neurosci. 35, 8004–8020 (2015).Article

Watanabe，S。等人，Prdm13调节视网膜无长突中间神经元的亚型规格并调节视觉敏感性。J、 神经科学。358004-8020（2015）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Sapkota, D. et al. Onecut1 and Onecut2 redundantly regulate early retinal cell fates during development. Proc. Nat. Acad. Sci. USA 111, E4086–95 (2014).Chan, C. S. et al. Cell type- and stage-specific expression of OTX2 is regulated by multiple transcription factors andcis-regulatory modules in the retina.

Sapkota，D。等人，Onecut1和Onecut2在发育过程中冗余地调节早期视网膜细胞的命运。程序。国家科学院。科学。美国111，E4086–95（2014）。Chan，C.S.等人。OTX2的细胞类型和阶段特异性表达受视网膜中多种转录因子和顺式调节模块的调节。

Development. 147, dev187922 (2020).Li, C., Virgilio, M. C., Collins, K. L. & Welch, J. D. Multi-omic single-cell velocity models epigenome–transcriptome interactions and improves cell fate prediction. Nat. Biotechnol. 41, 1–12 (2022).Maden, M. Retinoid signalling in the development of the Central Nervous System.

发展。147，dev187922（2020）。Li，C.，Virgilio，M.C.，Collins，K.L。和Welch，J.D。多组单细胞速度模型表观基因组-转录组相互作用并改善细胞命运预测。美国国家生物技术公司。41，1-12（2022）。Maden，M。中枢神经系统发育中的类视黄醇信号传导。

Nat. Rev. Neurosci. 3, 843–853 (2002).Article .

神经科学杂志。3843-853（2002）。文章。

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Behesti, H., Holt, J. K. & Sowden, J. C. The level of BMP4 signaling is critical for the regulation of distinct T-box gene expression domains and growth along the dorso-ventral axis of the optic cup. BMC Dev. Biol. 6, 62 (2006).Hadyniak, S. E. et al. Retinoic acid signaling regulates spatiotemporal specification of human green and Red Cones.

Behesti，H.，Holt，J.K。＆Sowden，J.C。BMP4信号传导水平对于调节不同的T-box基因表达域和沿视杯背腹轴的生长至关重要。BMC开发生物学。6，62（2006）。Hadyniak，S.E.等人。视黄酸信号调节人类绿色和红色视锥细胞的时空规格。

PLOS Biol. 22, e3002464 (2024).Lu, Y. et al. Single-cell analysis of human retina identifies evolutionarily conserved and species-specific mechanisms controlling development. Dev. Cell 53, 473–491 (2020).Kuht, H. J. et al. Genotypic and phenotypic spectrum of foveal hypoplasia. Ophthalmology 129, 708–718 (2022).Article .

《公共科学图书馆·生物学》。22，e3002464（2024）。Lu，Y.等人。人类视网膜的单细胞分析确定了控制发育的进化保守和物种特异性机制。Dev.Cell 53473-491（2020）。Kuht，H.J.等人。中央凹发育不全的基因型和表型谱。眼科129708-718（2022）。文章。

PubMed

PubMed

Google Scholar

谷歌学者

Watkins-Chow, D. E. et al. Mutation of the diamond-blackfan anemia gene rps7 in mouse results in morphological and neuroanatomical phenotypes. PLoS Genet. 9, e1003094 (2013).Oliver, E. R., Saunders, T. L., Tarlee, S. A. & Glaser, T. Ribosomal protein L24 defect in belly spot and tail (bst), a mouseminute.

Watkins Chow，D.E.等人。小鼠钻石-布莱克凡贫血基因rps7的突变导致形态学和神经解剖学表型。PLoS Genet。9，e1003094（2013）。Oliver，E.R.，Saunders，T.L.，Tarlee，S.A。＆Glaser，T。核糖体蛋白L24在小鼠腹部斑点和尾巴（bst）中的缺陷。

Development 131, 3907–3920 (2004).Article .

发展1313907-3920（2004）。文章。

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Owen, L. A. et al. The utah protocol for postmortem eye phenotyping and molecular biochemical analysis. Investigative Opthalmology Vis. Sci. 60, 1204 (2019).Article

Owen，L.A.等人，《犹他州死后眼表型和分子生化分析方案》。调查眼科Vis。科学。601204（2019）。文章

CAS

中科院

Google Scholar

谷歌学者

Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3587–3587 (2021).McGinnis, C. S., Murrow, L. M. & Gartner, Z. J. Doubletfinder: doublet detection in single-cell RNA sequencing data using artificial nearest neighbors. Cell Syst. 8, 329–337 (2019).Granja, J.

Hao，Y.等人。多模式单细胞数据的综合分析。细胞1843587-3587（2021）。McGinnis，C.S.，Murrow，L.M。＆Gartner，Z.J。Doubletfinder：使用人工最近邻在单细胞RNA测序数据中进行双重检测。细胞系统。8329-337（2019）。格兰贾，J。

M. et al. ARCHR is a scalable software package for integrative single-cell chromatin accessibility analysis. Nat. Genet. 53, 403–411 (2021).Article .

M、 ARCHR是一个可扩展的软件包，用于整合单细胞染色质可及性分析。纳特·吉内特。53403-411（2021）。文章。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Gayoso, A. et al. A python library for probabilistic analysis of single-cell omics data. Nat. Biotechnol. 2,163–166 (2022).Wolf, F. A., Angerer, P. & Theis, F. J. Scanpy: large-scale single-cell gene expression data analysis. Genome Biol. 19, 15 (2018).Lotfollahi, M., Naghipourfar, M., Luecken, M.D.

Gayoso，A。等人。用于单细胞组学数据概率分析的python库。美国国家生物技术公司。2163-166（2022）。Wolf，F.A.，Angerer，P。＆Theis，F.J。Scanpy：大规模单细胞基因表达数据分析。基因组生物学。19,15（2018）。Lotfollahi，M.，Naghipourfar，M.，Luecken，M.D。

et al. Mapping single-cell data to reference atlases by transfer learning. Nat. Biotechnol. 40, 121–130 (2022).Zheng, S. C. et al. Universal prediction of cell-cycle position using transfer learning. Genome Biol. 23, 41 (2022).Liang, Q. et al. A multi-omics atlas of the human retina at single-cell resolution.

等人。通过转移学习将单细胞数据映射到参考地图集。美国国家生物技术公司。40121-130（2022）。Zheng，S.C.等人。使用转移学习对细胞周期位置进行通用预测。基因组生物学。23，41（2022）。Liang，Q。等人。单细胞分辨率的人类视网膜多组学图谱。

Cell Genomics, 3, 100298 (2023).Trapnell, C. et al. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nat. Biotechnol. 32, 381–386 (2014).Article .

细胞基因组学，3100298（2023）。Trapnell，C。等人。通过单细胞的伪时间顺序揭示了细胞命运决定的动力学和调节因子。美国国家生物技术公司。32381-386（2014）。文章。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Qiu, X. et al. Reversed graph embedding resolves complex single-cell trajectories. Nat. Methods 14, 979–982 (2017).Article

Qiu，X。等人。反向图嵌入解决了复杂的单细胞轨迹。。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Cao, J. et al. The single-cell transcriptional landscape of mammalian organogenesis. Nature 566, 496–502 (2019).Article

Cao，J。等人。哺乳动物器官发生的单细胞转录景观。自然566496-502（2019）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Haghverdi, L., Lun, A. T., Morgan, M. D. & Marioni, J. C. Batch effects in single-cell RNA-sequencing data are corrected by matching mutual nearest neighbors. Nat. Biotechnol. 36, 421–427 (2018).Article

Haghverdi，L.，Lun，A.T.，Morgan，M.D。和Marioni，J.C。通过匹配相互最近的邻居来校正单细胞RNA测序数据中的批次效应。美国国家生物技术公司。36421-427（2018）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Levine, J. H. et al. Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis. Cell 162, 184–197 (2015).Article

Levine，J.H.等人。数据驱动的AML表型解剖揭示了与预后相关的祖细胞样细胞。细胞162184-197（2015）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

La Manno, G. et al. RNA velocity of single cells. Nature 560, 494–498 (2018).Article

La Manno，G。等人。单细胞的RNA速度。自然560494-498（2018）。文章

ADS

广告

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

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).Article

Bergen，V.，Lange，M.，Peidli，S.，Wolf，F.A。＆Theis，F.J。通过动力学建模将RNA速度推广到瞬时细胞状态。美国国家生物技术公司。381408-1414（2020）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

DeTomaso, D. & Yosef, N. Hotspot identifies informative gene modules across modalities of single-cell genomics. Cell Syst. 12, 446–456 (2021).Raudvere, U. et al. g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update). Nucleic Acids Res.

DeTomaso，D。＆Yosef，N。Hotspot跨单细胞基因组学模式识别信息丰富的基因模块。细胞系统。12446-456（2021）。Raudvere，U。等人g：Profiler：用于功能富集分析和基因列表转换的web服务器（2019年更新）。核酸研究。

47, W191–W198 (2019).Stuart, T., Srivastava, A., Madad, S., Lareau, C. A. & Satija, R. Single-cell chromatin state analysis with Signac. Nat. Methods 18, 1333–1341 (2021).Article .

47，W191–W198（2019）。Stuart，T.，Srivastava，A.，Madad，S.，Lareau，C.A。＆Satija，R。使用Signac进行单细胞染色质状态分析。自然方法181333-1341（2021）。文章。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Lawrence, M. et al. Software for computing and annotating genomic ranges. PLoS Computational Biol. 9, e1003118 (2013).Lange, M. et al. CellRank for directed single-cell fate mapping. Nat. Methods 19, 159–170 (2022).Article

Lawrence，M.等人。用于计算和注释基因组范围的软件。PLoS计算生物学。9，e1003118（2013）。Lange，M。等人。CellRank用于定向单细胞命运映射。自然方法19159-170（2022）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Schep, A. N., Wu, B., Buenrostro, J. D. & Greenleaf, W. J. chromVAR: inferring transcription-factor-associated accessibility from single-cell epigenomic data. Nat. Methods 14, 975–978 (2017).Zhang, Y. et al. Model-based analysis of ChIP-Seq (macs). Genome Biol. 9, R137 (2008).McLean, C.

Schep，A.N.，Wu，B.，Buenrostro，J.D。和Greenleaf，W.J.chromVAR：从单细胞表观基因组数据推断转录因子相关的可及性。自然方法14975-978（2017）。Zhang，Y.等人。ChIP-Seq（macs）的基于模型的分析。基因组生物学。9，R137（2008）。。

Y. et al. Great improves functional interpretation of cis-regulatory regions. Nat. Biotechnol. 28, 495–501 (2010).Article .

Y、 Great等人改进了顺式调控区的功能解释。美国国家生物技术公司。28495-501（2010）。文章。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Tanigawa, Y., Dyer, E. S. & Bejerano, G. WHICH TF is functionally important in your open chromatin data? PLOS Computational Biology 18, e1010378 (2022).Quinlan, A. R. & Hall, I. M. BEDTools: A flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).Article .

Tanigawa，Y.，Dyer，E.S。和Bejerano，G。哪种TF在您的开放染色质数据中功能上很重要？PLOS计算生物学18，e1010378（2022）。Quinlan，A.R。＆Hall，I.M。BEDTools：用于比较基因组特征的灵活实用程序套件。生物信息学26841-842（2010）。文章。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wang, J. et al. Single-cell multiomics of the human retina reveals hierarchical transcription factor collaboration in mediating cell type-specific effects of genetic variants on gene regulation. Genome Biol. 24, 269 (2023).Hinrichs, A. S. et al. The UCSC genome browser database: Update 2006.

Wang，J.等人。人类视网膜的单细胞多组学揭示了分层转录因子在介导遗传变异对基因调控的细胞类型特异性作用方面的协作。基因组生物学。24269（2023）。Hinrichs，A.S.等人，《UCSC基因组浏览器数据库：2006年更新》。

Nucleic Acids Res. 34, D590–8 (2006).Gharahkhani, P. et al. Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries. Nat. Commun. 12, 1258 (2021).Khawaja, A. P. et al. Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma.

核酸研究34，D590-8（2006）。Gharahkhani，P。等人。全基因组荟萃分析确定了127个开角型青光眼基因座，这些基因座在祖先之间具有一致的作用。国家公社。121258（2021）。Khawaja，A.P.等人的全基因组分析确定了68个与眼压相关的新基因座，并改善了原发性开角型青光眼的风险预测。

Nat. Genet. 50, 778–782 (2018).Article .

Nat.Genet。50, 778-782 (2018).第[UNK]条。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Springelkamp, H. et al. New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics. Hum. Mol. Genet. 26, 438–458 (2017).Khor, C. C. et al. Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma.

Springelkamp，H.等人。基于眼压和视盘特征的荟萃分析，对原发性开角型青光眼遗传学的新见解。嗯，摩尔·吉内特。26438-458（2017）。全基因组关联研究确定了原发性闭角型青光眼的五个新的易感基因座。

Nat. Genet. 48, 556–562 (2016).Article .

Nat.Genet。48, 556-562 (2016).第[UNK]条。

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Fritsche, L. G. et al. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat. Genet. 48, 134–143 (2015).Article

Fritsche，L.G。等人。一项针对年龄相关性黄斑变性的大型全基因组关联研究强调了罕见和常见变异的贡献。纳特·吉内特。48134-143（2015）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Canela-Xandri, O., Rawlik, K. & Tenesa, A. An atlas of genetic associations in UK Biobank. Nat. Genet. 50, 1593–1599 (2018).Article

Canela Xandri，O.，Rawlik，K。和Tenesa，A。英国生物库中的遗传关联图谱。纳特·吉内特。501593-1599（2018）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hysi, P. G. et al. Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia. Nat. Genet. 52, 401–407 (2020).Article

对542934名欧洲血统受试者的荟萃分析确定了易患屈光不正和近视的新基因和机制。纳特·吉内特。52401-407（2020）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Murphy, A. E., Schilder, B. M. & Skene, N. G. MungeSumstats: A bioconductor package for the standardization and quality control of many GWAS summary statistics. Bioinformatics 37, 4593–4596 (2021).Article

Murphy，A.E.，Schilder，B.M。＆Skene，N.G。MungeSumstats：用于许多GWAS摘要统计的标准化和质量控制的生物导体包。生物信息学374593-4596（2021）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

de Leeuw, C. A., Mooij, J. M., Heskes, T. & Posthuma, D. MAGMA: generalized gene-set analysis of GWAS data. PLOS Comput. Biol. 11, e1004219 (2015).Skene, N. G. & Grant, S. G. Identification of vulnerable cell types in major brain disorders using single cell transcriptomes and expression weighted cell type enrichment.

de Leeuw，C.A.，Mooij，J.M.，Heskes，T。和Posthuma，D。MAGMA：GWAS数据的广义基因组分析。PLOS计算机。生物学11，e1004219（2015）。Skene，N.G。＆Grant，S.G。使用单细胞转录组和表达加权细胞类型富集鉴定主要脑部疾病中的脆弱细胞类型。

Front. Neurosci. 10, 16 (2016).Skene, N. G. et al. Genetic identification of brain cell types underlying schizophrenia. Nat. Genet. 50, 825–833 (2018).Article .

正面。。10，16（2016）。Skene，N.G.等人。精神分裂症脑细胞类型的遗传鉴定。纳特·吉内特。50825-833（2018）。文章。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zuo, Z. Single cell dual-omic atlas of the human developing retina, github path zhenzuo2/human-developmental-retina-atlas.Preprint at Zenodo, https://doi.org/10.5281/zenodo.11250482 (2024).Download referencesAcknowledgementsThis work is part of the Human Cell Atlas (www.humancellatlas.org) and supported by Chan-Zuckerburg Foundation Grant CZF2021-237885 and CZF2019-002425, awarded to R.C.

Zuo，Z。人类发育视网膜的单细胞双组学图谱，github path zhenzuo2/人类发育视网膜图谱。Zenodo预印本，https://doi.org/10.5281/zenodo.11250482（2024年）。下载参考文献致谢这项工作是人类细胞图谱（www.humancellatlas.org）的一部分，并得到了授予R.C.的Chan Zuckerburg基金会资助CZF2021-237885和CZF2019-002425的支持。

We thank R.C., T.A.R, and A.M. for critically reading the manuscript. Thanks for data curation by Jennifer Zamanian. Thanks for the grammar editing by Aurian Maleki and David Rauch. Figure 1A and Supplementary Figs. 1A, 2A, 3A, 7K, and 9A were created with BioRender.com.Author informationAuthor notesThese authors contributed equally: Zhen Zuo, Xuesen Cheng, Salma Ferdous.Authors and AffiliationsHGSC, Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, USAZhen Zuo, Xuesen Cheng, Salma Ferdous, Jianming Shao, Jin Li, Yourong Bao, Jean Li, Jiaxiong Lu, Yumei Li & Rui ChenGraduate Program in Quantitative and Computational Biosciences, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, USAZhen Zuo & Rui ChenDepartment of Ophthalmology & Vision Science, UC Davis School of Medicine, 4860 Y St, Sacramento, CA, USAAntonio Jacobo Lopez & Ala MoshiriDepartment of Biological Structure, University of Washington, 1410 NE Campus Pkwy, Seattle, WA, USAJuliette Wohlschlegel, Aric Prieve & Thomas A.

。感谢Jennifer Zamanian的数据管理。感谢Aurian Maleki和David Rauch的语法编辑。图1A和补充图1A，2A，3A，7K和9A是用BioRender.com创建的。作者信息作者注意到这些作者做出了同样的贡献：Zhen Zuo，Xuesen Cheng，Salma Ferdous。作者和单位：德克萨斯州休斯顿贝勒广场1号贝勒医学院分子与人类遗传学系GSC，左乌萨真，郑学森，萨尔玛·费杜斯，邵建明，金丽，鲍友荣，李让，吕家雄，李玉梅和程睿，德克萨斯州休斯顿贝勒广场1号贝勒医学院定量与计算生物科学研究生项目，左乌萨真和陈睿加州大学戴维斯分校医学院眼科与视觉科学系，4860 Y St，萨克拉门托，加利福尼亚州，美国安东尼奥·雅各布·洛佩斯和阿拉·莫希里华盛顿大学生物结构系，1410年NE Campus Pkwy，西雅图，华盛顿州，美国Juliette Wohlschlegel，Aric Prieve&Thomas A。

RehUlverscroft Eye Unit, School of Psychology and Vision Sciences, The University of Leicester, Leicester, UKMervyn G. ThomasVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, USARui ChenGavin Herbert Eye Institute - Center for Translational Vision Research, De.

莱斯特大学心理学与视觉科学学院RehUlverscroft眼科，莱斯特，UKMervyn G.ThomasVerna和Marrs McLean，贝勒医学院生物化学与分子生物学系，德克萨斯州休斯顿贝勒广场1号，USARui ChenGavin Herbert眼科研究所-转化视觉研究中心，De。

PubMed Google ScholarXuesen ChengView author publicationsYou can also search for this author in

PubMed Google ScholarXuesen ChengView作者出版物您也可以在

PubMed Google ScholarSalma FerdousView author publicationsYou can also search for this author in

PubMed Google ScholarSalma FerdousView作者出版物您也可以在

PubMed Google ScholarJianming ShaoView author publicationsYou can also search for this author in

PubMed谷歌学者邵建明查看作者出版物您也可以在

PubMed Google ScholarJin LiView author publicationsYou can also search for this author in

PubMed Google ScholarJin LiView作者出版物您也可以在

PubMed Google ScholarYourong BaoView author publicationsYou can also search for this author in

PubMed Google ScholaryYourong BaoView作者出版物您也可以在

PubMed Google ScholarJean LiView author publicationsYou can also search for this author in

PubMed Google ScholarJean LiView作者出版物您也可以在

PubMed Google ScholarJiaxiong LuView author publicationsYou can also search for this author in

PubMed谷歌学者贾雄LuView作者出版物您也可以在

PubMed Google ScholarAntonio Jacobo LopezView author publicationsYou can also search for this author in

PubMed Google ScholarAntonio Jacobo LopezView作者出版物您也可以在

PubMed Google ScholarJuliette WohlschlegelView author publicationsYou can also search for this author in

PubMed Google ScholarJuliette WohlschlegelView作者出版物您也可以在

PubMed Google ScholarAric PrieveView author publicationsYou can also search for this author in

PubMed谷歌学术PrieveView作者出版物您也可以在

PubMed Google ScholarMervyn G. ThomasView author publicationsYou can also search for this author in

PubMed Google ScholarMervyn G.ThomasView作者出版物您也可以在

PubMed Google ScholarThomas A. RehView author publicationsYou can also search for this author in

PubMed Google ScholarThomas A.RehView作者出版物您也可以在

PubMed Google ScholarYumei LiView author publicationsYou can also search for this author in

PubMed Google ScholarYumei LiView作者出版物您也可以在

PubMed Google ScholarAla MoshiriView author publicationsYou can also search for this author in

PubMed Google ScholarAla MoshiriView作者出版物您也可以在

PubMed Google ScholarRui ChenView author publicationsYou can also search for this author in

PubMed Google ScholarContributionsR.C. conceived and supervised the project. A.M. and A.L. performed the sample collection. Y.L. and X.C. performed the single-nuclei dissociation and sequencing. Z.Z. performed the data analysis. Z.Z., R.C., and S.F. worked on writing, reviewing and editing.

PubMed谷歌学术贡献。C、 构思并监督了该项目。A、 M.和A.L.进行了样本采集。Y、 。Z、 Z.进行了数据分析。Z、 Z.，R.C。和S.F.致力于写作，评论和编辑。

T.A.R, J.W., and A.P. shared three early-time datasets. Jin.L. provided analysis support and made data available online. J.S. performed GWAS enrichment analysis. Y.B. and Jean.L. prepared Supplementary Data 8. Jiaxiong.L. confirmed the accuracy of Supplementary Data 8. M.T. provided Macular Hypoplasia Related Genes.

T、 A.R、J.W.和A.P.共享了三个早期数据集。金。五十、 提供分析支持并在线提供数据。J、 美国进行了GWAS富集分析。Y、 B.和琼。五十、 准备补充数据8。贾雄。五十、 证实了补充数据8的准确性。M、 T.提供了黄斑发育不全相关基因。

All authors approved the manuscript. All authors edited the manuscript.Corresponding authorCorrespondence to.

。所有作者都编辑了手稿。对应作者对应。

Rui Chen.Ethics declarations

。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Peer review

同行评审

Peer review information

同行评审信息

Nature Communications thanks Anand Swaroop, Zepeng Qu, Soumitra Pal and the other, anonymous, reviewer for their contribution to the peer review of this work. A peer review file is available.

Nature Communications感谢Anand Swaroop，Zepeng Qu，Soumitra Pal和另一位匿名审稿人对这项工作的同行评审做出的贡献。可以获得同行评审文件。

Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationSupplementary InformationPeer Review FileDescription of additional supplementary filesSupplementary Data 1Supplementary Data 2Supplementary Data 3Supplementary Data 4Supplementary Data 5Supplementary Data 6Supplementary Data 7Supplementary Data 8Supplementary Data 9Supplementary Data 10Supplementary Data 11Supplementary Data 12Reporting SummarySource dataSource DataRights and permissions.

Additional informationPublisher的注释Springer Nature在已发布的地图和机构隶属关系中的管辖权主张方面保持中立。补充信息补充信息同行评审文件其他补充文件的描述补充数据1补充数据2补充数据3补充数据4补充数据5补充数据6补充数据7补充数据8补充数据9补充数据10补充数据11补充数据12报告摘要源数据源数据权限。

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

开放获取本文是根据知识共享署名4.0国际许可证授权的，该许可证允许以任何媒体或格式使用，共享，改编，分发和复制，只要您对原始作者和来源给予适当的信任，提供知识共享许可证的链接，并指出是否进行了更改。

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

本文中的图像或其他第三方材料包含在文章的知识共享许可中，除非在材料的信用额度中另有说明。如果材料未包含在文章的知识共享许可中，并且您的预期用途不受法律法规的许可或超出许可用途，则您需要直接获得版权所有者的许可。

To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/..

要查看此许可证的副本，请访问http://creativecommons.org/licenses/by/4.0/..

Reprints and permissionsAbout this articleCite this articleZuo, Z., Cheng, X., Ferdous, S. et al. Single cell dual-omic atlas of the human developing retina.

转载和许可本文引用本文Zuo，Z.，Cheng，X.，Ferdous，S。等人。人类发育中视网膜的单细胞双组学图谱。

Nat Commun 15, 6792 (2024). https://doi.org/10.1038/s41467-024-50853-5Download citationReceived: 06 October 2023Accepted: 24 July 2024Published: 09 August 2024DOI: https://doi.org/10.1038/s41467-024-50853-5Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

《国家公社》156792（2024）。https://doi.org/10.1038/s41467-024-50853-5Download引文接收日期：2023年10月6日接收日期：2024年7月24日发布日期：2024年8月9日OI：https://doi.org/10.1038/s41467-024-50853-5Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

Provided by the Springer Nature SharedIt content-sharing initiative

由Springer Nature SharedIt内容共享计划提供

CommentsBy submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

评论通过提交评论，您同意遵守我们的条款和社区指南。如果您发现有虐待行为或不符合我们的条款或准则，请将其标记为不合适。