单细胞转录组分析揭示了小鼠早期视囊胚视网膜祖细胞在发育阶段的变化。

Single-cell transcriptional analysis reveals developmental stage-dependent changes in retinal progenitors in the murine early optic vesicle.

机构信息

Department of Veterinary Anatomy, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo, 113-8657, Japan; Department of Applied Biological Chemistry, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo, 113-8657, Japan; RNA Company Limited, Nishikamata 7-25-7, Ota-ku, Tokyo, 144-0051, Japan.

Department of Applied Biological Chemistry, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo, 113-8657, Japan.

出版信息

Biochem Biophys Res Commun. 2021 Mar 5;543:80-86. doi: 10.1016/j.bbrc.2021.01.043. Epub 2021 Feb 3.

DOI:10.1016/j.bbrc.2021.01.043

PMID:33548738

Abstract

The optic vesicle in the developing embryonic eye contains a multitude of neuroepithelial progenitors that subsequently differentiate into functionally distinct domains of the optic cup, such as the neural retina, pigment epithelium, and optic stalk. To investigate cell-type diversity across early optic vesicles before regionalization of the optic cup, we performed single-cell RNA-sequencing (scRNA-seq) using 7989 cells from the presumptive eye area in mouse embryos at the 12-26-somite stages at five developmental time points. We demonstrated the presence of seven optic vesicle populations. Moreover, the four populations of retinal progenitor cells could be classified according to their stage-dependent time point, and these cells exhibited altered expression of several structural and metabolic key genes, such as Col9a1 and Ckb, just before regionalization of the optic cup. From these data, we provide the first report on stage-dependent transcriptional profiles during initial retinal specification at single-cell resolution and highlight the unexpected developmental heterogeneity of the murine optic vesicle structure.

摘要

在发育中的胚胎眼睛的视泡中包含大量的神经上皮祖细胞，这些祖细胞随后分化为视杯的功能不同的区域，如神经视网膜、色素上皮和视柄。为了在视杯区域化之前研究早期视泡中的细胞类型多样性，我们在五个发育时间点对来自 12-26 体节阶段的小鼠胚胎的假定眼区的 7989 个细胞进行了单细胞 RNA 测序（scRNA-seq）。我们证明了存在七个视泡群体。此外，根据其在时间上的依赖性，四个视网膜祖细胞群体可以进行分类，这些细胞在视杯区域化之前表现出几个结构和代谢关键基因的表达发生改变，如 Col9a1 和 Ckb。从这些数据中，我们首次以单细胞分辨率报告了在初始视网膜特化过程中的阶段依赖性转录谱，并强调了小鼠视泡结构出人意料的发育异质性。