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Quick Commitment and Efficient Reprogramming Route of Direct Induction of Retinal Ganglion Cell-like Neurons.

Abstract：

:Direct reprogramming has been widely explored to generate various types of neurons for neurobiological research and translational medicine applications, but there is still no efficient reprogramming method to generate retinal ganglion cell (RGC)-like neurons, which are the sole projection neurons in the retina. Here, we show that three transcription factors, Ascl1, Brn3b, and Isl1, efficiently convert fibroblasts into RGC-like neurons (iRGCs). Furthermore, we show that the competence of cells to enter iRGC reprogramming route is determined by the cell-cycle status at a very early stage of the process. The iRGC reprogramming route involves intermediate states that are characterized by a transient inflammatory-like response followed by active epigenomic and transcriptional modifications. Our study provides an efficient method to generate iRGCs, which would be a valuable cell source for potential glaucoma cell replacement therapy and drug screening studies, and reveals the key cellular events that govern successful neuronal fate reprogramming.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Wang J,He Q,Zhang K,Sun H,Zhang G,Liang H,Guo J,Hao L,Ke J,Chen S

doi

10.1016/j.stemcr.2020.09.008

subject

Has Abstract

pub_date

2020-11-10 00:00:00

pages

1095-1110

issue

5

issn

2213-6711

pii

S2213-6711(20)30383-0

journal_volume

15

pub_type

杂志文章

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