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Cell Stem Cell. 2018 Oct 4;23(4):530-543.e9. doi: 10.1016/j.stem.2018.09.007.

Muscle Satellite Cell Cross-Talk with a Vascular Niche Maintains Quiescence via VEGF and Notch Signaling.

Author information

1
Medical Scientist Training Program, University of Minnesota Medical School, Minneapolis, MN, USA; Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN, USA; Paul & Sheila Wellstone Muscular Dystrophy Center, University of Minnesota Medical School, Minneapolis, MN, USA; Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA. Electronic address: verma014@umn.edu.
2
Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN, USA; Paul & Sheila Wellstone Muscular Dystrophy Center, University of Minnesota Medical School, Minneapolis, MN, USA; Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA.
3
University of Minnesota Informatics Institute, University of Minnesota Medical School, Minneapolis, MN, USA.
4
San Raffaele Telethon Institute for Gene Therapy, Milan, Italy.
5
Institut NeuroMyoGene, Université de Lyon, Lyon, France.
6
Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN, USA; Paul & Sheila Wellstone Muscular Dystrophy Center, University of Minnesota Medical School, Minneapolis, MN, USA; Department of Ophthalmology and Visual Neurosciences, University of Minnesota Medical School, Minneapolis, MN, USA.
7
Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN, USA; Paul & Sheila Wellstone Muscular Dystrophy Center, University of Minnesota Medical School, Minneapolis, MN, USA; Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA. Electronic address: asakura@umn.edu.

Abstract

Skeletal muscle is a complex tissue containing tissue resident muscle stem cells (satellite cells) (MuSCs) important for postnatal muscle growth and regeneration. Quantitative analysis of the biological function of MuSCs and the molecular pathways responsible for a potential juxtavascular niche for MuSCs is currently lacking. We utilized fluorescent reporter mice and muscle tissue clearing to investigate the proximity of MuSCs to capillaries in 3 dimensions. We show that MuSCs express abundant VEGFA, which recruits endothelial cells (ECs) in vitro, whereas blocking VEGFA using both a vascular endothelial growth factor (VEGF) inhibitor and MuSC-specific VEGFA gene deletion reduces the proximity of MuSCs to capillaries. Importantly, this proximity to the blood vessels was associated with MuSC self-renewal in which the EC-derived Notch ligand Dll4 induces quiescence in MuSCs. We hypothesize that MuSCs recruit capillary ECs via VEGFA, and in return, ECs maintain MuSC quiescence though Dll4.

KEYWORDS:

Dll4; Notch; VEGF; endothelial cell; niche; satellite cell; skeletal muscle; stem cell; tissue clearing; vasculature

PMID:
30290177
PMCID:
PMC6178221
DOI:
10.1016/j.stem.2018.09.007
[Indexed for MEDLINE]
Free PMC Article

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