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Oscillations of Delta-like1 regulate the balance between differentiation and maintenance of muscle stem cells

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Item Type:Article
Title:Oscillations of Delta-like1 regulate the balance between differentiation and maintenance of muscle stem cells
Creators Name:Zhang, Y. and Lahmann, I. and Baum, K. and Shimojo, H. and Mourikis, P. and Wolf, J. and Kageyama, R. and Birchmeier, C.
Abstract:Cell-cell interactions mediated by Notch are critical for the maintenance of skeletal muscle stem cells. However, dynamics, cellular source and identity of functional Notch ligands during expansion of the stem cell pool in muscle growth and regeneration remain poorly characterized. Here we demonstrate that oscillating Delta-like 1 (Dll1) produced by myogenic cells is an indispensable Notch ligand for self-renewal of muscle stem cells in mice. Dll1 expression is controlled by the Notch target Hes1 and the muscle regulatory factor MyoD. Consistent with our mathematical model, our experimental analyses show that Hes1 acts as the oscillatory pacemaker, whereas MyoD regulates robust Dll1 expression. Interfering with Dll1 oscillations without changing its overall expression level impairs self-renewal, resulting in premature differentiation of muscle stem cells during muscle growth and regeneration. We conclude that the oscillatory Dll1 input into Notch signaling ensures the equilibrium between self-renewal and differentiation in myogenic cell communities.
Keywords:Calcium-Binding Proteins, Cell Differentiation, Developmental Gene Expression Regulation, HEK293 Cells, Knockout Mice, Muscle Development, Muscles, Mutation, MyoD Protein, Signal Transduction, Stem Cells, Transcription Factor HES-1, Transcriptome, Animals, Mice
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:1318
Date:26 February 2021
Additional Information:Erratum in: Nat Commun 12(1): 1766.
Official Publication:https://doi.org/10.1038/s41467-021-21631-4
PubMed:View item in PubMed

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