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

Stem Cell Research
Aishwarya G NadadhurVivi M Heine

Abstract

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 ...Continue Reading

Citations

May 16, 2019·Assay and Drug Development Technologies·Veronica Porterfield
Sep 4, 2020·Proceedings of the National Academy of Sciences of the United States of America·Eleanor C WarrenRobin S B Williams
Aug 23, 2019·Annals of Neurology·Prisca S LeferinkVivi M Heine
Aug 28, 2021·Biology·Philip Jalink, Massimiliano Caiazzo
Aug 30, 2021·Stem Cell Research·Stephanie D Beekhuis-HoekstraVivi M Heine

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