@article{99f78dc2205a42f88a70867ea52e3b4d,
title = "Dedifferentiation-derived neural stem cells exhibit perturbed temporal progression",
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.",
keywords = "dedifferentiation, Drosophila, neuroblast, temporal transcription factors, terminal differentiation",
author = "Kellie Veen and Nguyen, \{Phuong Khanh\} and Francesca Froldi and Qian Dong and Edel Alvarez-Ochoa and Harvey, \{Kieran F.\} and McMullen, \{John P.D.\} and Owen Marshall and Jusuf, \{Patricia R.\} and Cheng, \{Louise Y.\}",
note = "Funding Information: We are grateful to C. Desplan, H. Richardson, S.Russell, X Li, U.Walldorf, K Saito, for generous sharing of antibodies and fly stocks. LYC is funded by an Australian Research Council (ARC) Future Fellowship (FT180100255), LYC's laboratory is supported by funding from the National Health and Medical Research Council of Australia (NHMRC 1182847), Australian Research Council (190101743) and the Peter MacCallum Cancer Foundation. KFH was supported by an NHMRC Investigator grant (APP1194467) and Australian Research Council (190101743). Confocal Microscopy was performed at the Centre for Advanced Histology \& Microscopy (CAHM) at the Peter MacCallum Cancer Centre and the Biological Optical Microscopy Platform at the University of Melbourne. We thank CAHM and Research Laboratory Support Services and acknowledge support to them by the Peter MacCallum Cancer Foundation and the Australian Cancer Research Foundation. Open access publishing facilitated by The University of Melbourne, as part of the Wiley - The University of Melbourne agreement via the Council of Australian University Librarians. Funding Information: We are grateful to C. Desplan, H. Richardson, S.Russell, X Li, U.Walldorf, K Saito, for generous sharing of antibodies and fly stocks. LYC is funded by an Australian Research Council (ARC) Future Fellowship (FT180100255), LYC's laboratory is supported by funding from the National Health and Medical Research Council of Australia (NHMRC 1182847), Australian Research Council (190101743) and the Peter MacCallum Cancer Foundation. KFH was supported by an NHMRC Investigator grant (APP1194467) and Australian Research Council (190101743). Confocal Microscopy was performed at the Centre for Advanced Histology \& Microscopy (CAHM) at the Peter MacCallum Cancer Centre and the Biological Optical Microscopy Platform at the University of Melbourne. We thank CAHM and Research Laboratory Support Services and acknowledge support to them by the Peter MacCallum Cancer Foundation and the Australian Cancer Research Foundation. Open access publishing facilitated by The University of Melbourne, as part of the Wiley ‐ The University of Melbourne agreement via the Council of Australian University Librarians. Publisher Copyright: {\textcopyright} 2023 The Authors. Published under the terms of the CC BY 4.0 license.",
year = "2023",
month = jun,
day = "5",
doi = "10.15252/embr.202255837",
language = "English",
volume = "24",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "EMBO Press",
number = "6",
}