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An oscillatory network controlling self-renewal of skeletal muscle stem cells

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Item Type:Review
Title:An oscillatory network controlling self-renewal of skeletal muscle stem cells
Creators Name:Lahmann, I. and Zhang, Y. and Baum, K. and Wolf, J. and Birchmeier, C.
Abstract:The balance between proliferation and differentiation of muscle stem cells is tightly controlled, ensuring the maintenance of a cellular pool needed for muscle growth and repair. Muscle stem cells can proliferate, they can generate differentiating cells, or they self-renew to produce new stem cells. Notch signaling plays a crucial role in this process. Recent studies revealed that expression of the Notch effector HES1 oscillates in activated muscle stem cells. The oscillatory expression of HES1 periodically represses transcription from the genes encoding the myogenic transcription factor MYOD and the Notch ligand DLL1, thereby driving MYOD and DLL1 oscillations. This oscillatory network allows muscle progenitor cells and activated muscle stem cells to remain in a proliferative and 'undecided' state, in which they can either differentiate or self-renew. When HES1 is downregulated, MYOD oscillations become unstable and are replaced by sustained expression, which drives the cells into terminal differentiation. During development and regeneration, proliferating stem cells contact each other and the stability of the oscillatory expression depends on regular DLL1 inputs provided by neighboring cells. In such communities of cells that receive and provide Notch signals, the appropriate timing of DLL1 inputs is important, as sustained DLL1 cannot replace oscillatory DLL1. Thus, in cell communities, DLL1 oscillations ensure the appropriate balance between self-renewal and differentiation. In summary, oscillations in myogenic cells are an important example of dynamic gene expression determining cell fate.
Keywords:Notch Signaling, MyoD, Hes1, Dll1, Myogenesis, Myogenic Differentiation
Source:Experimental Cell Research
Page Range:112933
Date:15 December 2021
Additional Information:Copyright © 2021 Elsevier Inc. All rights reserved. This manuscript version is made available under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-nd/4.0/ or send a letter to Creative Commons, PO Box 1866, Mountain View, CA 94042, USA.
Official Publication:https://doi.org/10.1016/j.yexcr.2021.112933
PubMed:View item in PubMed

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