Homo- and heterodimerization of bHLH transcription factors balance stemness with bipotential differentiation in the Drosophila gut
Homo- and heterodimerization of bHLH transcription factors balance stemness with bipotential differentiation in the Drosophila gut
ABSTRACT Multipotent adult stem cells must balance self-renewal with differentiation into various mature cell types. How this balance is regulated at the transcriptional level is poorly understood. Here we show that a network of basic Helix-Loop-Helix (bHLH) transcription factors controls both stemness and bi-potential differentiation in the Drosophila adult intestine. We find that homodimers of Daughterless (Da), homolog of mammalian E proteins, maintain the self-renewal of intestinal stem cells (ISCs), and antagonise the activity of heterodimers of Da and Scute (Sc), homolog of ASCL and a known regulator of intestinal secretory differentiation. The HLH factor Extramacrochaetae (Emc), homologous to Id proteins, promotes absorptive differentiation by titrating Da and Sc to. We further show that Emc prevents the committed absorptive progenitor (the enteroblast, EB) from de-differentiating, underscoring the plasticity of these cells. Switching physical interaction partners in this way enables the active maintenance of stemness while priming stem cells for differentiation along two alternative fates. Such regulatory logic could be recapitulated in other bipotent stem cell systems.
Nirello Vinicius Dias、Azami Sina、Varga-Weisz Patrick、Korzelius Jerome、Edgar Bruce A.、Puig-Barbe Aleix、de Navascu¨|s Joaqu¨an、Dettmann Svenja
International Laboratory for Microbiome Host Epigenetics, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of CampinasMax Planck Institute for Biology of AgeingInternational Laboratory for Microbiome Host Epigenetics, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas||School of Life Sciences, University of EssexMax Planck Institute for Biology of Ageing||DKFZ/ZMBH Alliance, University of Heidelberg||School of Biosciences, University of KentDKFZ/ZMBH Alliance, University of Heidelberg||Huntsman Cancer Institute & Dept. of Oncological Sciences, University of UtahEuropean Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Hadyn Ellis Building||EMBL-European Bioinformatics Institute, Wellcome Genome CampusEuropean Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Hadyn Ellis Building||School of Life Sciences, University of EssexDKFZ/ZMBH Alliance, University of Heidelberg||AbbVie Germany GmbH & Co. KG
分子生物学细胞生物学遗传学
bHLHstemnessdifferentiationbipotent stem cellintestinal stem cell
Nirello Vinicius Dias,Azami Sina,Varga-Weisz Patrick,Korzelius Jerome,Edgar Bruce A.,Puig-Barbe Aleix,de Navascu¨|s Joaqu¨an,Dettmann Svenja.Homo- and heterodimerization of bHLH transcription factors balance stemness with bipotential differentiation in the Drosophila gut[EB/OL].(2025-03-28)[2025-05-01].https://www.biorxiv.org/content/10.1101/685347.点此复制
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