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

Publication date: 21 March 2017
Source:Cell Reports, Volume 18, Issue 12
Author(s): Tomoko Yamazaki, Ani Nalbandian, Yutaka Uchida, Wenling Li, Thomas D. Arnold, Yoshiaki Kubota, Seiji Yamamoto, Masatsugu Ema, Yoh-suke Mukouyama
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.

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Teaser

Yamazaki et al. describe an unanticipated role of tissue-localized myeloid progenitors in pericyte development in the ectoderm-derived skin. The developmental sources of dermal pericytes are heterogeneous, and a portion of dermal pericytes has a hematopoietic/myeloid origin. Moreover, pericytes differentiate from tissue-localized myeloid progenitors through TGF-β signaling.


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