Generation of self-organized sensory ganglion organoids and retinal ganglion cells from fibroblasts.

Abstract:

:Neural organoids provide a powerful tool for investigating neural development, modeling neural diseases, screening drugs, and developing cell-based therapies. Somatic cells have previously been reprogrammed by transcription factors (TFs) into sensory ganglion (SG) neurons but not SG organoids. We identify a combination of triple TFs Ascl1, Brn3b/3a, and Isl1 (ABI) as an efficient means to reprogram mouse and human fibroblasts into self-organized and networked induced SG (iSG) organoids. The iSG neurons exhibit molecular features, subtype diversity, electrophysiological and calcium response properties, and innervation patterns characteristic of peripheral sensory neurons. Moreover, we have defined retinal ganglion cell (RGC)-specific identifiers to demonstrate the ability for ABI to reprogram induced RGCs (iRGCs) from fibroblasts. Unlike iSG neurons, iRGCs maintain a scattering distribution pattern characteristic of endogenous RGCs. iSG organoids may serve as a model to decipher the pathogenesis of sensorineural diseases and screen effective drugs and a source for cell replacement therapy.

journal_name

Sci Adv

journal_title

Science advances

authors

Xiao D,Deng Q,Guo Y,Huang X,Zou M,Zhong J,Rao P,Xu Z,Liu Y,Hu Y,Shen Y,Jin K,Xiang M

doi

10.1126/sciadv.aaz5858

subject

Has Abstract

pub_date

2020-05-29 00:00:00

pages

eaaz5858

issue

22

issn

2375-2548

pii

aaz5858

journal_volume

6

pub_type

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