中国科学院重庆绿色智能技术研究院机构知识库

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	Acute brain vascular regeneration occurs via lymphatic transdifferentiation
	Chen, Jingying1,2; Li, Xiuhua1; Ni, Rui1; Chen, Qi1; Yang, Qifen1; He, Jianbo1; Luo, Lingfei1,2
	2021-11-22
摘要	Acute ischemic stroke damages the regional brain blood vessel (BV) network. Acute recovery of basic blood flows, which is carried out by the earliest regenerated BVs, are critical to improve clinical outcomes and minimize lethality. Although the late-regenerated BVs form via growing along the meninge-derived ingrown lymphatic vessels (iLVs), mechanisms underlying the early, acute BV regeneration remain elusive. Using zebrafish cerebrovascular injury models, we show that the earliest regenerated BVs come from lymphatic trans differentiation, a hitherto unappreciated process in vertebrates. Mechanistically, the LV-to-BV transdifferentiation occurs exclusively in the stand-alone iLVs through Notch activation. In the track iLVs adhered by late regenerated BVs, transdifferentiation never occurs because the BV-expressing EphrinB2a paracellularly activates the iLV-expressing EphB4a to inhibit Notch activation. Suppression of LV-to-BV transdifferentiation blocks acute BV regeneration and becomes lethal. These results demonstrate that acute BV regeneration occurs via lymphatic transdifferentiation, suggesting this process and key regulatory molecules EphrinB2a/ EphB4a/Notch as new postischemic therapeutic targets.
DOI	10.1016/j.devcel.2021.09.005
发表期刊	DEVELOPMENTAL CELL
ISSN	1534-5807
卷号	56期号:22页码:3115-+
通讯作者	Luo, Lingfei(lluo@swu.edu.cn)
收录类别	SCI
WOS记录号	WOS:000730205700001
语种	英语