Nakajima Hiroyuki, Ishikawa Hiroyuki, Yamamoto Takuya, Chiba Ayano, Fukui Hajime, Sako Keisuke, Fukumoto Moe, Mattonet Kenny, Kwon Hyouk-Bum, Hui Subhra P, Dobreva Gergana D, Kikuchi Kazu, Helker Christian S M, Stainier Didier Y R, Mochizuki Naoki
Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 564-8565, Japan.
Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 564-8565, Japan.
Dev Cell. 2023 Feb 6;58(3):224-238.e7. doi: 10.1016/j.devcel.2022.12.013. Epub 2023 Jan 23.
Endothelial cells (ECs) line blood vessels and serve as a niche for hematopoietic stem and progenitor cells (HSPCs). Recent data point to tissue-specific EC specialization as well as heterogeneity; however, it remains unclear how ECs acquire these properties. Here, by combining live-imaging-based lineage-tracing and single-cell transcriptomics in zebrafish embryos, we identify an unexpected origin for part of the vascular HSPC niche. We find that islet1 (isl1)-expressing cells are the progenitors of the venous ECs that constitute the majority of the HSPC niche. These isl1-expressing cells surprisingly originate from the endoderm and differentiate into ECs in a process dependent on Bmp-Smad signaling and subsequently requiring npas4l (cloche) function. Single-cell RNA sequencing analyses show that isl1-derived ECs express a set of genes that reflect their distinct origin. This study demonstrates that endothelial specialization in the HSPC niche is determined at least in part by the origin of the ECs.
内皮细胞（ECs）排列在血管内壁，为造血干细胞和祖细胞（HSPCs）提供微环境。最近的数据表明组织特异性内皮细胞具有特化以及异质性；然而，内皮细胞如何获得这些特性仍不清楚。在这里，通过结合基于活体成像的谱系追踪和斑马鱼胚胎中的单细胞转录组学，我们确定了部分血管HSPC微环境的意外起源。我们发现，表达胰岛1（isl1）的细胞是构成大部分HSPC微环境的静脉内皮细胞的祖细胞。这些表达isl1的细胞惊人地起源于内胚层，并在依赖于骨形态发生蛋白-信号转导和转录激活因子（Bmp-Smad）信号传导的过程中分化为内皮细胞，随后需要神经元 PAS 域蛋白 4 样蛋白（npas4l，即克洛什蛋白）发挥功能。单细胞RNA测序分析表明，源自isl1的内皮细胞表达一组反映其独特起源的基因。这项研究表明，HSPC微环境中的内皮细胞特化至少部分由内皮细胞的起源决定。
