Blood endothelial ALK1-BMP4 signaling axis regulates adult hair follicle stem cell activation

EMBO J. 2023 May 15;42(10):e112196. doi: 10.15252/embj.2022112196. Epub 2023 Mar 30.

Abstract

Blood vessels can play dual roles in tissue growth by transporting gases and nutrients and by regulating tissue stem cell activity via signaling. Correlative evidence implicates skin endothelial cells (ECs) as signaling niches of hair follicle stem cells (HFSCs), but functional demonstration from gene depletion of signaling molecules in ECs is missing to date. Here, we show that depletion of the vasculature-factor Alk1 increases BMP4 secretion from ECs, which delays HFSC activation. Furthermore, while previous evidence suggests a lymphatic vessel role in adult HFSC activation possibly through tissue drainage, a blood vessel role has not yet been addressed. Genetic perturbation of the ALK1-BMP4 axis in all ECs or the lymphatic ECs specifically unveils inhibition of HFSC activation by blood vessels. Our work suggests a broader relevance of blood vessels, adding adult HFSCs to the EC functional repertoire as signaling niches for the adult stem cells.

Keywords: Alk1; BMP4; endothelial cells; hair follicle stem cells; vascular niche.

Publication types

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

MeSH terms

  • Activin Receptors, Type II* / genetics
  • Activin Receptors, Type II* / metabolism
  • Adult Stem Cells*
  • Animals
  • Bone Morphogenetic Protein 4* / genetics
  • Bone Morphogenetic Protein 4* / metabolism
  • Endothelial Cells
  • Hair Follicle*
  • Mice
  • Signal Transduction
  • Stem Cells

Substances

  • Acvrl1 protein, mouse
  • Bmp4 protein, mouse
  • Activin Receptors, Type II
  • Bone Morphogenetic Protein 4

Associated data

  • GEO/GSE211381
  • GEO/GSE223723