Tracing the first hematopoietic stem cell generation in human embryo by single-cell RNA sequencing

作者：Yang Zeng, Jian He, Zhijie Bai, Zongcheng Li, Yandong Gong, Chen Liu, Yanli Ni, Junjie Du, Chunyu Ma, Lihong Bian, Yu Lan, Bing Liu · 发表于：Cell Research · 年份：2019 · DOI：10.1038/s41422-019-0228-6 · 被引用次数：209 · 研究领域：Zebrafish Biomedical Research Applications、Single-cell and spatial transcriptomics、Immune cells in cancer

Abstract Tracing the emergence of the first hematopoietic stem cells (HSCs) in human embryos, particularly the scarce and transient precursors thereof, is so far challenging, largely due to the technical limitations and the material rarity. Here, using single-cell RNA sequencing, we constructed the first genome-scale gene expression landscape covering the entire course of endothelial-to-HSC transition during human embryogenesis. The transcriptomically defined HSC-primed hemogenic endothelial cells (HECs) were captured at Carnegie stage (CS) 12–14 in an unbiased way, showing an unambiguous feature of arterial endothelial cells (ECs) with the up-regulation of RUNX1 , MYB and ANGPT1 . Importantly, subcategorizing CD34 + CD45 − ECs into a CD44 + population strikingly enriched HECs by over 10-fold. We further mapped the developmental path from arterial ECs via HSC-primed HECs to hematopoietic stem progenitor cells, and revealed a distinct expression pattern of genes that were transiently over-represented upon the hemogenic fate choice of arterial ECs, including EMCN , PROCR and RUNX1T1 . We also uncovered another temporally and molecularly distinct intra-embryonic HEC population, which was detected mainly at earlier CS 10 and lacked the arterial feature. Finally, we revealed the cellular components of the putative aortic niche and potential cellular interactions acting on the HSC-primed HECs. The cellular and molecular programs that underlie the generation of the first HSCs from H...