Tissue Myeloid Progenitors Differentiate into Pericytes through TGF-β Signaling in Developing Skin Vasculature.
Tissue Myeloid Progenitors Differentiate into Pericytes through TGF-β Signaling in Developing Skin Vasculature.
复制标题
DOI：
10.1016/j.celrep.2017.02.069
复制
发表时间：
2017-03-21
期刊：
影响因子：
8.8
通讯作者：
Mukouyama YS
中科院分区：
文献类型：
--
作者：
Yamazaki T;Nalbandian A;Uchida Y;Li W;Arnold TD;Kubota Y;Yamamoto S;Ema M;Mukouyama YS
壁细胞（周细胞和血管平滑肌细胞）对于调节血管网络和维持血管完整性是必不可少的，但它们的起源在不同组织中是不同的，并且在来自外胚层的器官（如皮肤）中是未知的。在这里，我们表明，组织本地化的骨髓祖细胞有助于胚胎皮肤血管周细胞的发展。一系列体内命运作图实验表明，组织髓样祖细胞分化为周细胞。此外，PU.1突变体中组织髓样细胞及其祖细胞的耗竭导致周细胞发育缺陷。来自胚胎皮肤的FACS分离的髓样细胞及其祖细胞在培养中分化成周细胞。在分子水平上，转化生长因子-β（TGF-β）诱导培养物中的周细胞分化。此外，2型TGF-β受体（Tgfbr 2）突变体在皮肤脉管系统中表现出周细胞发育缺陷。总之，这些数据表明周细胞通过TGF-β信号传导从皮肤脉管系统中的组织髓样祖细胞分化。Yamazaki等人描述了组织定位的髓样祖细胞在外胚层衍生的皮肤和脑中周细胞发育中的意外作用。真皮周细胞的发育来源是异质的，并且一部分真皮周细胞具有造血/髓样起源。此外，周细胞通过TGF-β信号传导与组织定位的骨髓祖细胞分化。
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 mutants results in defective pericyte development. 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, type2 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. Yamazaki et al. describe an unanticipated role of tissue-localized myeloid progenitors in pericyte development in the ectoderm-derived skin and brain. 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.