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

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 demonstra...

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Veröffentlicht in:Nature communications Jg. 12; H. 1; S. 1318 - 16
Hauptverfasser: Zhang, Yao, Lahmann, Ines, Baum, Katharina, Shimojo, Hiromi, Mourikis, Philippos, Wolf, Jana, Kageyama, Ryoichiro, Birchmeier, Carmen
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 26.02.2021
Nature Publishing Group
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Schlagworte:
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Animals
Calcium-Binding Proteins - genetics
Calcium-Binding Proteins - metabolism
Cell differentiation
Cell Differentiation - physiology
Cell interactions
Cell self-renewal
DELTA protein
Female
Gene Expression Regulation, Developmental
HEK293 Cells
Humanities and Social Sciences
Humans
Life Sciences
Ligands
Maintenance
Mathematical models
Mice
Mice, Knockout
multidisciplinary
Muscle Development - genetics
Muscle Development - physiology
Muscle regulatory factor
Muscles
Muscles - metabolism
Mutation
MyoD protein
MyoD Protein - genetics
MyoD Protein - metabolism
Oscillations
Pacemakers
Regeneration
Robustness (mathematics)
Science
Science (multidisciplinary)
Signal Transduction - physiology
Skeletal muscle
Stem cell transplantation
Stem cells
Stem Cells - physiology
Surgical implants
Transcription
Transcription Factor HES-1 - metabolism
Transcriptome
ISSN:2041-1723, 2041-1723
Online-Zugang:Volltext
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Beschreibung
Zusammenfassung: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. The cell source and dynamics of Notch ligands during the regulation of muscle stem cells is unclear. Here, the authors show that the Notch ligand Dll1 has to oscillate in order to control the balance between self-renewal and differentiation of muscle stem cells, with Hes1 acting as transcriptional pacemaker for the oscillatory network.
Bibliographie:ObjectType-Article-1
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-21631-4