胚胎干细胞中 Hes1 的缺失导致视网膜色素上皮形态发生和特化的发育障碍。

Loss of Hes1 in embryonic stem cells caused developmental disorders in retinal pigment epithelium morphogenesis and specification.

机构信息

NHC Key Laboratory of Human Stem and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China; Hunan International Scientific and Technological Cooperation Base of Development and Carcinogenesis, Changsha, China.

NHC Key Laboratory of Human Stem and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China; Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China.

出版信息

Biochem Biophys Res Commun. 2022 Dec 3;632:76-84. doi: 10.1016/j.bbrc.2022.09.080. Epub 2022 Sep 24.

DOI:10.1016/j.bbrc.2022.09.080

PMID:36206597

Abstract

Hairy and enhancer of split homolog-1 (Hes1) is a member of an extensive family of basic helix-loop-helix (bHLH) proteins and plays a crucial role in neurogenesis, myogenesis, hematopoiesis, and sex determination. It has been reported that Hes1 is essential for precursors maintenance, optic cup-stalk boundary maintenance, and morphogenesis of the retina. However, it still reminds questions about the role and mechanism of Hes1 in the development of retinal pigment epithelial cells. In our study, We generated Hes1 human embrsyonic stem cells, and attempted to induce them into retinal pigment epithelial cells by our previous protocol, found that the cells induced by Hes1 hESCs hardly expressed RPE-related genes, and rarely appeared RPE cell morphology. Additionally, Hes1 may affect the development of RPE cells via Wnt4 pathway by analyzing the RNA-seq data of differently expressed genes between normal RPE cells development and Hes1 RPE cells development. Overall, depletion of Hes1 may result in the failure of Wnt4 signal activation, and contributed to the developmental disorder in retinal pigment epithelium morphogenesis and specification.

摘要

Hairy 和 enhancer of split 同源物-1（Hes1）是广泛存在的碱性螺旋-环-螺旋（bHLH）蛋白家族的一员，在神经发生、肌发生、造血和性别决定中发挥着关键作用。据报道，Hes1 对于前体细胞的维持、视杯柄边界的维持以及视网膜的形态发生是必需的。然而，它仍然存在关于 Hes1 在视网膜色素上皮细胞发育中的作用和机制的问题。在我们的研究中，我们生成了 Hes1 人类胚胎干细胞，并试图按照我们之前的方案将其诱导为视网膜色素上皮细胞，发现由 Hes1 hESCs 诱导的细胞几乎不表达与 RPE 相关的基因，并且很少出现 RPE 细胞形态。此外，通过分析正常 RPE 细胞发育和 Hes1 RPE 细胞发育之间差异表达基因的 RNA-seq 数据，我们发现 Hes1 可能通过 Wnt4 途径影响 RPE 细胞的发育。总的来说，Hes1 的缺失可能导致 Wnt4 信号激活失败，导致视网膜色素上皮形态发生和特化的发育障碍。