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

Aishwarya G. Nadadhur, Prisca S. Leferink, Dwayne Holmes, Lisa Hinz, Paulien Cornelissen-Steijger, Lisa Gasparotto, Vivi M. Heine

Research output: Contribution to JournalArticleAcademicpeer-review

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 in vitro. This challenges the utility of generic neural induction procedures, while highlighting the importance of carefully selecting specific NP protocols.

Original languageEnglish
Pages (from-to)25-34
Number of pages10
JournalStem Cell Research
Volume32
Early online date23 Aug 2018
DOIs
Publication statusPublished - Oct 2018

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Neural Inhibition
Tretinoin
Astrocytes
Phenotype
Pluripotent Stem Cells
Neural Tube
Neuroglia
Stem Cells
Pregnancy
Population
In Vitro Techniques

Keywords

  • Astrocytes
  • In vitro
  • Neural progenitors
  • Neurons
  • Patterning factors
  • Pluripotent stem cells

Cite this

Nadadhur, Aishwarya G. ; Leferink, Prisca S. ; Holmes, Dwayne ; Hinz, Lisa ; Cornelissen-Steijger, Paulien ; Gasparotto, Lisa ; Heine, Vivi M. / Patterning factors during neural progenitor induction determine regional identity and differentiation potential in vitro. In: Stem Cell Research. 2018 ; Vol. 32. pp. 25-34.
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Patterning factors during neural progenitor induction determine regional identity and differentiation potential in vitro. / Nadadhur, Aishwarya G.; Leferink, Prisca S.; Holmes, Dwayne; Hinz, Lisa; Cornelissen-Steijger, Paulien; Gasparotto, Lisa; Heine, Vivi M.

In: Stem Cell Research, Vol. 32, 10.2018, p. 25-34.

Research output: Contribution to JournalArticleAcademicpeer-review

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