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解析眼表外胚层分化系统中的动态单细胞转录图谱。

Deciphering the dynamic single-cell transcriptional landscape in the ocular surface ectoderm differentiation system.

作者信息

Zhang Canwei, Lin Zesong, Yu Yankun, Wu Siqi, Huang Huaxing, Huang Ying, Liu Jiafeng, Mo Kunlun, Tan Jieying, Han Zhuo, Li Mingsen, Zhao Wei, Ouyang Hong, Chen Xiangjun, Wang Li

机构信息

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangzhou 510060, China.

Department of Ophthalmology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan 250014, China.

出版信息

Life Med. 2024 Sep 5;3(5):lnae033. doi: 10.1093/lifemedi/lnae033. eCollection 2024 Oct.

DOI:10.1093/lifemedi/lnae033
PMID:39872440
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11749776/
Abstract

The ocular surface ectoderm (OSE) is essential for the development of the ocular surface, yet the molecular mechanisms driving its differentiation are not fully understood. In this study, we used single-cell transcriptomic analysis to explore the dynamic cellular trajectories and regulatory networks during the differentiation of embryonic stem cells (ESCs) into the OSE lineage. We identified nine distinct cell subpopulations undergoing differentiation along three main developmental branches: neural crest, neuroectodermal, and surface ectodermal lineages. Key marker gene expression, transcription factor activity, and signaling pathway insights revealed stepwise transitions from undifferentiated ESCs to fate-specified cell types, including a PAX6 + TP63 + population indicative of OSE precursors. Comparative analysis with mouse embryonic development confirmed the model's accuracy in mimicking epiblast-to-surface ectoderm dynamics. By integrating temporal dynamics of transcription factor activation and cell-cell communication, we constructed a comprehensive molecular atlas of the differentiation pathway from ESCs to distinct ectodermal lineages. This study provides new insights into the cellular heterogeneity and regulatory mechanisms of OSE development, aiding the understanding of ocular surface biology and the design of cell-based therapies for ocular surface disorders.

摘要

眼表外胚层（OSE）对于眼表的发育至关重要，但其分化的分子机制尚未完全明确。在本研究中，我们采用单细胞转录组分析来探索胚胎干细胞（ESC）向OSE谱系分化过程中的动态细胞轨迹和调控网络。我们鉴定出九个不同的细胞亚群，它们沿着三个主要发育分支进行分化：神经嵴、神经外胚层和表面外胚层谱系。关键标记基因表达、转录因子活性和信号通路分析揭示了从未分化的ESC向命运指定细胞类型的逐步转变，包括一个指示OSE前体的PAX6+TP63+群体。与小鼠胚胎发育的比较分析证实了该模型在模拟上胚层到表面外胚层动态过程中的准确性。通过整合转录因子激活的时间动态和细胞间通讯，我们构建了一个从ESC到不同外胚层谱系分化途径的综合分子图谱。本研究为OSE发育的细胞异质性和调控机制提供了新的见解，有助于理解眼表生物学以及设计针对眼表疾病的细胞疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f7/11749776/c7d68b13fd6b/lnae033_fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f7/11749776/ba2d7c965dcc/lnae033_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f7/11749776/25cf51808433/lnae033_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f7/11749776/0f27f30a55a6/lnae033_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f7/11749776/4480b36c5592/lnae033_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f7/11749776/eaf2dd3819f6/lnae033_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f7/11749776/cd022807f099/lnae033_fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f7/11749776/c7d68b13fd6b/lnae033_fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f7/11749776/ba2d7c965dcc/lnae033_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f7/11749776/25cf51808433/lnae033_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f7/11749776/0f27f30a55a6/lnae033_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f7/11749776/4480b36c5592/lnae033_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f7/11749776/eaf2dd3819f6/lnae033_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f7/11749776/cd022807f099/lnae033_fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3f7/11749776/c7d68b13fd6b/lnae033_fig7.jpg

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