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

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. • The absence of Hes 1 caused developmental disorders in RPE in morphogenesis and specification. • Lake of Hes1 in the differentiation of RPE showed premature neural precursors. • The depletion of Hes1 expression blocked the up-regulation expression of RPE-specific genes. • The up-regulation failure of the Wnt4 pathway emerged during RPE development by Hes1 deletion. [ABSTRACT FROM AUTHOR]