Dedifferentiation-derived neural stem cells exhibit perturbed temporal progression

Veen, K; Nguyen, PK; Froldi, F; Dong, Q; Alvarez-Ochoa, E; Harvey, KF; McMullen, JP; Marshall, O; Jusuf, PR; Cheng, LY

Author(s): Veen, K; Nguyen, PK; Froldi, F; Dong, Q; Alvarez-Ochoa, E; Harvey, KF; McMullen, JP; Marshall, O; Jusuf, PR; Cheng, LY;
Details: Publication Year 2023-06-05,Volume 24,Issue #6,Page e55837
Journal Title: EMBO Reports
Publication Type: Research article
Abstract: Dedifferentiation is the reversion of mature cells to a stem cell-like fate, whereby gene expression programs are altered and genes associated with multipotency are (re)expressed. Misexpression of multipotency factors and pathways causes the formation of ectopic neural stem cells (NSCs). Whether dedifferentiated NSCs faithfully produce the correct number and types of progeny, or undergo timely terminal differentiation, has not been assessed. Here, we show that ectopic NSCs induced via bHLH transcription factor Deadpan (Dpn) expression fail to undergo appropriate temporal progression by constantly expressing mid-temporal transcription factor(tTF), Sloppy-paired 1/2 (Slp). Consequently, this resulted in impaired terminal differenation and generated an excess of Twin of eyeless (Toy)-positive neurons at the expense of Reversed polarity (Repo)-positive glial cells. Preference for a mid-temporal fate in these ectopic NSCs is concordant with an enriched binding of Dpn at mid-tTF loci and a depletion of Dpn binding at early- and late-tTF loci. Retriggering the temporal series via manipulation of the temporal series or cell cycle is sufficient to reinstate neuronal diversity and timely termination.
Publisher: EMBO Press
Keywords: *Drosophila Proteins/genetics; *Neural Stem Cells/metabolism; Transcription Factors/metabolism; Neurons/metabolism; Neuroglia; Cell Differentiation/genetics; Gene Expression Regulation, Developmental; Drosophila; dedifferentiation; neuroblast; temporal transcription factors; terminal differentiation
Department(s): Laboratory Research
PubMed ID: 37039033
Publisher's Version: https://doi.org/10.15252/embr.202255837
Open Access at Publisher's Site: https://doi.org/10.15252/embr.202255837
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-08-07 07:16:21

Last Modified: 2023-08-07 07:17:40