Tracing the first hematopoietic stem cell generation in human embryo by single-cell RNA sequencing
Tracing the first hematopoietic stem cell generation in human embryo by single-cell RNA sequencing
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通过单细胞 RNA 测序追踪人类胚胎中第一代造血干细胞
DOI：
10.1038/s41422-019-0228-6
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发表时间：
2019-11-01
期刊：
影响因子：
44.1
通讯作者：
Liu, Bing
中科院分区：
文献类型：
--
作者：
Zeng, Yang;He, Jian;Liu, Bing
迄今为止，追踪人类胚胎中第一批造血干细胞（hsc）的出现，特别是其稀缺和短暂的前体，是具有挑战性的，主要是由于技术限制和材料稀缺。在这里，我们使用单细胞RNA测序，构建了第一个基因组尺度的基因表达图谱，涵盖了人类胚胎发生过程中内皮细胞向hsc转变的整个过程。在卡内基期（CS） 12-14时，以一种公正的方式捕获了转录组学定义的hsc引发的造血内皮细胞（HECs），显示了runx1，MYBandANGPT1上调的动脉内皮细胞（ECs）的明确特征。重要的是，将CD34+CD45−ECs亚分类为CD44+人群，显著富集了10倍以上的HECs。我们进一步绘制了从动脉内皮细胞通过hsc引发的hec到造血干细胞祖细胞的发育路径，并揭示了在动脉内皮细胞的造血命运选择中短暂过度代表的基因的独特表达模式，包括emcn，PROCRandRUNX1T1。我们还发现了另一个时间和分子上不同的胚胎内HEC群体，主要在CS 10早期检测到，缺乏动脉特征。最后，我们揭示了假定的主动脉生态位的细胞成分以及作用于hsc引发的hec的潜在细胞相互作用。人类胚胎中从造血干细胞产生第一批造血干细胞的细胞和分子程序，以及区分造血干细胞引发的造血干细胞与其他造血干细胞的能力，将阐明从多能干细胞生产临床有用的造血干细胞的策略。
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 ofRUNX1,MYBandANGPT1. 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, includingEMCN,PROCRandRUNX1T1. 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 HECs in human embryos, together with the ability to distinguish the HSC-primed HECs from others, will shed light on the strategies for the production of clinically useful HSCs from pluripotent stem cells.