A subset of cerebrovascular pericytes originates from mature macrophages in the very early phase of vascular development in CNS.
A subset of cerebrovascular pericytes originates from mature macrophages in the very early phase of vascular development in CNS.
复制标题
DOI：
10.1038/s41598-017-03994-1
复制
发表时间：
2017-06-20
影响因子：
4.6
通讯作者：
Sasahara M
中科院分区：
文献类型：
--
作者：
Yamamoto S;Muramatsu M;Azuma E;Ikutani M;Nagai Y;Sagara H;Koo BN;Kita S;O'Donnell E;Osawa T;Takahashi H;Takano KI;Dohmoto M;Sugimori M;Usui I;Watanabe Y;Hatakeyama N;Iwamoto T;Komuro I;Takatsu K;Tobe K;Niida S;Matsuda N;Shibuya M;Sasahara M
周细胞被认为起源于间充质细胞或神经嵴细胞。最近有报道称，周细胞在中枢神经系统（CNS）中发挥重要作用，通过调节血脑屏障稳态和毛细血管水平的血流。然而，CNS微血管周细胞的起源及其募集机制尚不清楚。在这里，我们展示了神经发生过程中脑血管周细胞的新来源。在胚胎10.5天小鼠胚胎的中枢神经系统中，在发育中的中脑背中线周围的无血管区观察到CD31+F4/80+造血系细胞。这些细胞表达额外的巨噬细胞标记物，如CD206和CD11b。此外，CD31+F4/80+细胞吞噬凋亡细胞成为功能成熟的巨噬细胞，粘附在新形成的心室下血管丛上，然后分裂成子细胞。最终，这些CD31+F4/80+细胞转分化为表达NG2/PDGFRβ/desmin的脑血管周细胞，包裹并结合血管内皮细胞。这些数据表明，一部分脑血管周细胞来源于中枢神经系统血管发育早期的成熟巨噬细胞，这些巨噬细胞又通过血流从胚胎造血部位（如卵黄囊）募集。
Pericytes are believed to originate from either mesenchymal or neural crest cells. It has recently been reported that pericytes play important roles in the central nervous system (CNS) by regulating blood-brain barrier homeostasis and blood flow at the capillary level. However, the origin of CNS microvascular pericytes and the mechanism of their recruitment remain unknown. Here, we show a new source of cerebrovascular pericytes during neurogenesis. In the CNS of embryonic day 10.5 mouse embryos, CD31+F4/80+ hematopoietic lineage cells were observed in the avascular region around the dorsal midline of the developing midbrain. These cells expressed additional macrophage markers such as CD206 and CD11b. Moreover, the CD31+F4/80+ cells phagocytosed apoptotic cells as functionally matured macrophages, adhered to the newly formed subventricular vascular plexus, and then divided into daughter cells. Eventually, these CD31+F4/80+ cells transdifferentiated into NG2/PDGFRβ/desmin-expressing cerebrovascular pericytes, enwrapping and associating with vascular endothelial cells. These data indicate that a subset of cerebrovascular pericytes derive from mature macrophages in the very early phase of CNS vascular development, which in turn are recruited from sites of embryonic hematopoiesis such as the yolk sac by way of blood flow.