Patterning factors during neural progenitor induction determine regional identity and differentiation potential in vitro - ScienceDirect

Stem Cell Research

Dwayne Holmes^2¹  Aishwarya G. Nadadhur^1²  Prisca S. Leferink^2,1³ 

[1] Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, the Netherlands^3;Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, the Netherlands^1;Pediatric Neurology, Emma Children's Hospital, Amsterdam UMC, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, the Netherlands^2

关键词: Neural progenitors;    Patterning factors;    In vitro;    Pluripotent stem cells;    Astrocytes;    Neurons;   

DOI  :  10.1016/j.scr.2018.08.017

学科分类：生物科学（综合）

来源: Elsevier

【 摘 要 】

The neural tube consists of neural progenitors (NPs) that acquire different characteristics during gestation due to patterning factors. However, the influence of such patterning factors on human pluripotent stem cells (hPSCs) during in vitro neural differentiation is often unclear. This study compared neural induction protocols involving in vitro patterning with single SMAD inhibition (SSI), retinoic acid (RA) administration and dual SMAD inhibition (DSI). While the derived NP cells expressed known NP markers, they differed in their NP expression profile and differentiation potential. Cortical neuronal cells generated from 1) SSI NPs exhibited less mature neuronal phenotypes, 2) RA NPs exhibited an increased GABAergic phenotype, and 3) DSI NPs exhibited greater expression of glutamatergic lineage markers. Further, although all NPs generated astrocytes, astrocytes derived from the RA-induced NPs had the highest GFAP expression. Differences between NP populations included differential expression of regional identity markers HOXB4, LBX1, OTX1 and GSX2, which persisted into mature neural cell stages. This study suggests that patterning factors regulate how potential NPs may differentiate into specific neuronal and glial cell types in vitro. This challenges the utility of generic neural induction procedures, while highlighting the importance of carefully selecting specific NP protocols.

【 授权许可】

Unknown