美国加州大学洛杉矶分校Hanna K. A. Mikkola、Vincenzo Calvanese等研究人员，合作绘制出人类造血干细胞从造血内皮到出生的图谱。相关论文于2022年4月13日在线发表在《自然》杂志上。

研究人员创建了一个人类造血组织的单细胞转录组图，从最早的妊娠到出生，并发现造血干细胞（HSC）特征RUNX1+HOXA9+MLLT3+MECOM+HLF+SPINK2+在整个妊娠期将HSC与祖先区分开来。除了主动脉-性腺-脾脏区域外，新生的HSC在6周时定植于肝脏之前，还在胎盘和卵黄囊中繁殖。对不同成熟阶段的HSC进行比较，研究人员发现HSC的转录因子机器是在HSC出现后建立的，而它们的表面表型在整个发育过程中不断变化。HSC向肝脏的过渡标志着一种分子转变，反映新生HSC身份的表面抗原被抑制，并获得了HSC的成熟标志CD133（由PROM1编码）和HLA-DR。HSC的起源被追踪到ALDH1A1+KCNK17+成血内皮细胞，该细胞来自IL33+ALDH1A1+动脉内皮亚群，称为成血前内皮细胞。

利用空间转录组学和免疫荧光，研究人员在位于腹腔的主动脉内造血细胞群中看到了这一过程。人类HSC发育图谱验证了从人类多能干细胞中产生的类似于主动脉-性腺-肾脏的确定性HSC和祖细胞，并作为改善其成熟为功能性HSC的指南。

据了解，由于无法确定造血干细胞在不同造血部位出现和成熟时的情况，因此人类HSC的发育过程界定得很差。

附：英文原文

Title: Mapping human haematopoietic stem cells from haemogenic endothelium to birth

Author: Calvanese, Vincenzo, Capellera-Garcia, Sandra, Ma, Feiyang, Fares, Iman, Liebscher, Simone, Ng, Elizabeth S., Ekstrand, Sophia, Aguad-Gorgori, Jlia, Vavilina, Anastasia, Lefaudeux, Diane, Nadel, Brian, Li, Jacky Y., Wang, Yanling, Lee, Lydia K., Ardehali, Reza, Iruela-Arispe, M. Luisa, Pellegrini, Matteo, Stanley, Ed G., Elefanty, Andrew G., Schenke-Layland, Katja, Mikkola, Hanna K. A.

Issue&Volume: 2022-04-13

Abstract: The ontogeny of human haematopoietic stem cells (HSCs) is poorly defined owing to the inability to identify HSCs as they emerge and mature at different haematopoietic sites1. Here we created a single-cell transcriptome map of human haematopoietic tissues from the first trimester to birth and found that the HSC signature RUNX1+HOXA9+MLLT3+MECOM+HLF+SPINK2+ distinguishes HSCs from progenitors throughout gestation. In addition to the aorta–gonad–mesonephros region, nascent HSCs populated the placenta and yolk sac before colonizing the liver at 6 weeks. A comparison of HSCs at different maturation stages revealed the establishment of HSC transcription factor machinery after the emergence of HSCs, whereas their surface phenotype evolved throughout development. The HSC transition to the liver marked a molecular shift evidenced by suppression of surface antigens reflecting nascent HSC identity, and acquisition of the HSC maturity markers CD133 (encoded by PROM1) and HLA-DR. HSC origin was tracked to ALDH1A1+KCNK17+ haemogenic endothelial cells, which arose from an IL33+ALDH1A1+ arterial endothelial subset termed pre-haemogenic endothelial cells. Using spatial transcriptomics and immunofluorescence, we visualized this process in ventrally located intra-aortic haematopoietic clusters. The in vivo map of human HSC ontogeny validated the generation of aorta–gonad–mesonephros-like definitive haematopoietic stem and progenitor cells from human pluripotent stem cells, and serves as a guide to improve their maturation to functional HSCs.

DOI: 10.1038/s41586-022-04571-x

Source: https://www.nature.com/articles/s41586-022-04571-x