Zuo Zhen, Cheng Xuesen, Ferdous Salma, Shao Jianming, Li Jin, Bao Yourong, Li Jean, Lu Jiaxiong, Jacobo Lopez Antonio, Wohlschlegel Juliette, Prieve Aric, Thomas Mervyn G, Reh Thomas A, Li Yumei, Moshiri Ala, Chen Rui
HGSC, Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, USA.
Graduate Program in Quantitative and Computational Biosciences, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX, USA.
Nat Commun. 2024 Aug 9;15(1):6792. doi: 10.1038/s41467-024-50853-5.
The 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. 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. 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.
视网膜的发育受到严格的时间和空间控制。为了深入了解这一过程的分子基础,我们构建了人类发育中视网膜的单核双组学图谱,该图谱包含来自14个孕龄在8至23周的人类胚胎和胎儿的约220,000个细胞核,并匹配了黄斑和周边组织。该图谱涵盖了视网膜中的所有主要细胞类型,以及很大一部分祖细胞和细胞类型特异性前体。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特化后期的分层发育的转变。我们鉴定出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。黄斑和周边视网膜之间的比较表明,它们在很大程度上具有一致但又不同的发育模式。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及相关疾病提供了宝贵资源。