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Continual inactivation of genes involved in stem cell functional identity stabilizes progenitor commitment

Noemi Rives-Quinto, Hideyuki Komori, Derek H. Janssens, Shu Kondo, Qi Dai, Adrian W. Moore, View ORCID ProfileCheng-Yu Lee
doi: https://doi.org/10.1101/2020.02.03.931972
Noemi Rives-Quinto
1Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA
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Hideyuki Komori
1Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA
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Derek H. Janssens
1Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA
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Shu Kondo
2Invertebrate Genetics Laboratory, National Institute of Genetics, Shizuoka, Japan
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Qi Dai
3Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden
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Adrian W. Moore
4Riken Center for Brain Science, Saitama, Japan
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Cheng-Yu Lee
1Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA
5Division of Genetic Medicine, Department of Internal Medicine; Department of Cell and Developmental Biology; and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109 USA
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  • ORCID record for Cheng-Yu Lee
  • For correspondence: leecheng@umich.edu
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Summary

Expansion of the pool of stem cells that indirectly generate differentiated cells through intermediate progenitors drives vertebrate brain evolution. Due to a lack of lineage information, mechanistic investigation of the competency of stem cells to generate intermediate progenitors remains impossible. Fly larval brain neuroblasts provide excellent in vivo models for investigating the regulation of stem cell functionality during neurogenesis. Type II neuroblasts undergo indirect neurogenesis by dividing asymmetrically to generate a neuroblast and a progeny that commits to an intermediate progenitor (INP) identity. We identified Tailless (Tll) as the master regulator that maintains type II neuroblast functional identity, including the competency to generate INPs. Successive inactivation during INP commitment inhibits tll activation by Notch, preventing INPs from reacquiring neuroblast functionality. We propose that the continual inactivation of neural stem cell functional identity genes by histone deacetylation allows intermediate progenitors to stably commit to generating diverse differentiated cells during indirect neurogenesis.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 16, 2020.
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Continual inactivation of genes involved in stem cell functional identity stabilizes progenitor commitment
Noemi Rives-Quinto, Hideyuki Komori, Derek H. Janssens, Shu Kondo, Qi Dai, Adrian W. Moore, Cheng-Yu Lee
bioRxiv 2020.02.03.931972; doi: https://doi.org/10.1101/2020.02.03.931972
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Continual inactivation of genes involved in stem cell functional identity stabilizes progenitor commitment
Noemi Rives-Quinto, Hideyuki Komori, Derek H. Janssens, Shu Kondo, Qi Dai, Adrian W. Moore, Cheng-Yu Lee
bioRxiv 2020.02.03.931972; doi: https://doi.org/10.1101/2020.02.03.931972

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