Tissue Myeloid Progenitors Differentiate into Pericytes through TGF-β Signaling in Developing Skin Vasculature

Cell Rep. 2017 Mar 21;18(12):2991-3004. doi: 10.1016/j.celrep.2017.02.069.


Mural cells (pericytes and vascular smooth muscle cells) are essential for the regulation of vascular networks and maintenance of vascular integrity, but their origins are diverse in different tissues and not known in the organs that arise from the ectoderm, such as skin. Here, we show that tissue-localized myeloid progenitors contribute to pericyte development in embryonic skin vasculature. A series of in vivo fate-mapping experiments indicates that tissue myeloid progenitors differentiate into pericytes. Furthermore, depletion of tissue myeloid cells and their progenitors in PU.1 (also known as Spi1) mutants results in defective pericyte development. Fluorescence-activated cell sorting (FACS)-isolated myeloid cells and their progenitors from embryonic skin differentiate into pericytes in culture. At the molecular level, transforming growth factor-β (TGF-β) induces pericyte differentiation in culture. Furthermore, type 2 TGF-β receptor (Tgfbr2) mutants exhibit deficient pericyte development in skin vasculature. Combined, these data suggest that pericytes differentiate from tissue myeloid progenitors in the skin vasculature through TGF-β signaling.

Keywords: TGF-β; brain; capillary blood vessel; fate mapping; mural cell; myeloid; pericyte; skin; tissue macrophage; vascular development.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Lineage
  • Cells, Cultured
  • Dermis / cytology
  • Embryo, Mammalian / cytology
  • Hematopoiesis
  • Mice, Inbred C57BL
  • Muscle, Smooth, Vascular / cytology
  • Myeloid Progenitor Cells / cytology*
  • Myeloid Progenitor Cells / metabolism*
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / metabolism
  • Neovascularization, Physiologic
  • Pericytes / cytology*
  • Signal Transduction*
  • Skin / blood supply*
  • Skin / embryology*
  • Transforming Growth Factor beta / metabolism*


  • Transforming Growth Factor beta