Endoderm-derived islet1-expressing cells differentiate into endothelial cells to function as the vascular HSPC niche in zebrafish

Endoderm-derived islet1-expressing cells differentiate into endothelial cells to function as the vascular HSPC niche in zebrafish
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DOI:
10.1016/j.devcel.2022.12.013
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发表时间:
2023-02-06
期刊:
影响因子:
11.8
通讯作者:
Mochizuki,Naoki
Mochizuki,Naoki
中科院分区:
生物学1区
文献类型:
--
作者:
Nakajima,Hiroyuki;Ishikawa,Hiroyuki;Mochizuki,Naoki

文献摘要

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血管内皮细胞(ECs)排列在血管内,是造血干细胞和祖细胞(HSPC)的利基。最近的数据表明EC具有组织特异性和异质性;然而,ECs是如何获得这些特性的还不清楚。在这里,通过结合基于实时成像的谱系追踪和斑马鱼胚胎的单细胞转录,我们确定了部分血管HSPC生态位的意想不到的来源。我们发现,表达ISL1的细胞是构成HSPC生态位的静脉内皮细胞的祖细胞。令人惊讶的是,这些表达1的细胞起源于内胚层,并在一个依赖于BMP-Smad信号的过程中分化为内皮细胞,随后需要npas4l(Cloche)功能。单细胞RNA测序分析表明,来源于1的内皮细胞表达一组反映其不同起源的基因。这项研究表明,HSPC生态位中内皮细胞的特化至少部分由内皮细胞的来源决定。
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 thatislet1(isl1)-expressing cells are the progenitors of the venous ECs that constitute the majority of the HSPC niche. Theseisl1-expressing cells surprisingly originate from the endoderm and differentiate into ECs in a process dependent on Bmp-Smad signaling and subsequently requiringnpas4l(cloche) function. Single-cell RNA sequencing analyses show thatisl1-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.