Global Transcriptional and Epigenetic Reconfiguration during Chemical Reprogramming of Human Retinal Pigment Epithelial Cells into Photoreceptor-like Cells

doi:10.3390/cells11193146

	Global Transcriptional and Epigenetic Reconfiguration during Chemical Reprogramming of Human Retinal Pigment Epithelial Cells into Photoreceptor-like Cells
	Deng, Xiaoqian 1,2; Lee, Ryan 2; Lim, Sin Yee 2; Zhong, Zheng 3; Wang, Jing 2; Liu, Yizhi 1; Fan, Guoping2,4
	2022-10
发表期刊	CELLS
EISSN	2073-4409
卷号	11 期号:19
发表状态	已发表
DOI	10.3390/cells11193146
摘要	Retinal degenerative diseases are frequently caused by the loss of retinal neural cells such as photoreceptors. Cell replacement is regarded as one of the most promising therapies. Multiple types of stem and somatic cells have been tested for photoreceptor conversion. However, current induction efficiencies are still low and the molecular mechanisms underlying reprogramming remain to be clarified. In this work, by combining treatment with small molecules, we directly reprogrammed human fetal retinal pigment epithelial (RPE) cells into chemically induced photoreceptor-like cells (CiPCs) in vitro. Bulk and single-cell RNA sequencing, as well as methylation sequencing, were performed to understand the transcriptional and epigenetic changes during CiPCs conversion. A multi-omics analysis showed that the direct reprogramming process partly resembled events of early retina development. We also found that the efficiency of CiPCs conversion from RPE is much better than that from human dermal fibroblasts (HDF). The small molecules effectively induced RPE cells into CiPCs via suppression of the epithelial-to-mesenchymal transition (EMT). Among the signaling pathways involved in CiPCs conversion, glutamate receptor activation is prominent. In summary, RPE cells can be efficiently reprogrammed into photoreceptor-like cells through defined pharmacological modulations, providing a useful cell source for photoreceptor generation in cell replacement therapy for retinal degenerative diseases.
关键词	human retinal pigment epithelial cells photoreceptor-like cells chemical reprogramming single-cell RNA sequencing DNA methylation sequencing
URL	查看原文
收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China (NSFC)[31871288]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000866749600001
出版者	MDPI
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/240484
专题	免疫化学研究所_特聘教授组_范国平组
通讯作者	Wang, Jing; Liu, Yizhi; Fan, Guoping
作者单位	1.Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangdong Prov Key Lab Ophthalmol & Visual Sci, Guangzhou 510060, Peoples R China 2.Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA 3.Univ Calif San Diego, Dept NanoEngn, La Jolla, CA 92093 USA 4.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China
通讯作者单位	免疫化学研究所
推荐引用方式 GB/T 7714	Deng, Xiaoqian,Lee, Ryan,Lim, Sin Yee,et al. Global Transcriptional and Epigenetic Reconfiguration during Chemical Reprogramming of Human Retinal Pigment Epithelial Cells into Photoreceptor-like Cells[J]. CELLS,2022,11(19).
APA	Deng, Xiaoqian.,Lee, Ryan.,Lim, Sin Yee.,Zhong, Zheng.,Wang, Jing.,...&Fan, Guoping.(2022).Global Transcriptional and Epigenetic Reconfiguration during Chemical Reprogramming of Human Retinal Pigment Epithelial Cells into Photoreceptor-like Cells.CELLS,11(19).
MLA	Deng, Xiaoqian,et al."Global Transcriptional and Epigenetic Reconfiguration during Chemical Reprogramming of Human Retinal Pigment Epithelial Cells into Photoreceptor-like Cells".CELLS 11.19(2022).