Dedifferentiation-derived neural stem cells exhibit perturbed temporal progression

Kellie Veen, Phuong Khanh Nguyen, Francesca Froldi, Qian Dong, Edel Alvarez-Ochoa, Kieran F. Harvey, John P.D. McMullen, Owen Marshall, Patricia R. Jusuf, Louise Y. Cheng

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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.

Original languageEnglish
Article numbere55837
Number of pages19
JournalEMBO Reports
Volume24
Issue number6
DOIs
Publication statusPublished - 5 Jun 2023

Keywords

  • dedifferentiation
  • Drosophila
  • neuroblast
  • temporal transcription factors
  • terminal differentiation

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