Tissue-localized myeloid progenitors differentiate into pericytes through TGF-β signaling in the developing vasculature

Authors

• T Yamazaki
• A Nalbandian
• Y Uchida
• W Li
• TD Arnold
• Y Kubota
• M Ema
• Y Mukouyama

Abstract

Multiple vascular cell types (endothelial cells, pericytes, and vascular smooth muscle cells) assemble to form an elaborate pattern of vascular network in organ-specific manners. Whether tissue-localized non-vascular cells are involved in organ-specific vascular development remains to be fully elucidated. Here we show that tissue-localized myeloid progenitors give rise to pericytes in the vasculature of the ectoderm-derived tissues such as skin and brain. A series of in vivo fate-mapping experiments revealed that myeloid progenitors generate pericytes during development. Furthermore, depletion of myeloid cells and their progenitors in PU.1 mutants results in defective pericyte development. Indeed, the mutants fail to develop the blood brain barrier. At mechanistic level, FACS-isolated F4/80+ myeloid progenitors from embryonic skin differentiate into NG2+ and PDGFRβ+ pericytes in response to transforming growth factor (TGF)-β. Moreover, conditional type2 TGF-β receptor (Tgfbr2) mutants exhibited deficient pericyte development in skin. Combined, these data suggest that myeloid progenitors differentiate into pericytes through TGF-β signaling in the embryonic skin and brain vasculature. This discovery may have profound implications for the study of pathological angiogenesis in wound healing and cancer.

Scientific Focus Area: Developmental Biology

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