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

Mayank Verma, Yoko Asakura, Bhavani Sai Rohit Murakonda, Thomas Pengo, Claire Latroche, Benedicte Chazaud, Linda K McLoon, Atsushi Asakura

Research output: Contribution to journalArticle

18 Citations (Scopus)

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. Verma et al. performed skeletal muscle tissue clearing and unbiased fluorescent image analysis to show that muscle stem cells (satellite cells) pattern the microvasculature to be in close proximity to them via VEGFA. In turn, this juxtavascular niche keeps the satellite cells in a more quiescent state, suggesting a beneficial cross-talk.

Original languageEnglish (US)
Pages (from-to)530-543.e9
JournalCell Stem Cell
Volume23
Issue number4
DOIs
StatePublished - Oct 4 2018

Fingerprint

Muscle Cells
Vascular Endothelial Growth Factor A
Blood Vessels
Endothelial Cells
Muscles
Skeletal Muscle
Stem Cells
Gene Deletion
Microvessels
Regeneration
Ligands
Growth

Keywords

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

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

Muscle Satellite Cell Cross-Talk with a Vascular Niche Maintains Quiescence via VEGF and Notch Signaling. / Verma, Mayank; Asakura, Yoko; Murakonda, Bhavani Sai Rohit; Pengo, Thomas; Latroche, Claire; Chazaud, Benedicte; McLoon, Linda K; Asakura, Atsushi.

In: Cell Stem Cell, Vol. 23, No. 4, 04.10.2018, p. 530-543.e9.

Research output: Contribution to journalArticle

Verma, Mayank ; Asakura, Yoko ; Murakonda, Bhavani Sai Rohit ; Pengo, Thomas ; Latroche, Claire ; Chazaud, Benedicte ; McLoon, Linda K ; Asakura, Atsushi. / Muscle Satellite Cell Cross-Talk with a Vascular Niche Maintains Quiescence via VEGF and Notch Signaling. In: Cell Stem Cell. 2018 ; Vol. 23, No. 4. pp. 530-543.e9.
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