剑桥大学Sam Behjati、Elisa Laurenti、Sarah A. Teichmann 和英国纽卡斯尔大学Muzlifah Haniffa研究组合作解码了人类胎儿肝脏造血功能。 这一研究成果在线发表在2019年10月9号的《自然》上。

研究人员对约140,000个肝脏和74,000个皮肤以及肾脏和卵黄囊细胞进行单细胞转录组测序，确定了人类血液和免疫细胞在发育过程中的组成。研究者从造血干细胞和多能祖细胞（HSC / MPP）推断分化轨迹，并评估组织微环境对血液和免疫细胞发育的影响。研究揭示了胎儿皮肤中的生理性红细胞生成以及卵黄囊中肥大细胞，自然杀伤细胞和先天性淋巴样细胞前体的存在。

研究还证明了在妊娠过程中胎儿肝脏的造血成分发生了变化，其远离了主要的类红细胞，同时伴随着HSC / MPPs分化潜能的平行变化，研究人员并对此进行了功能验证。该研究揭示的胎儿肝脏造血综合图谱为研究儿科血液和免疫疾病提供了蓝图，并为HSC / MPP的治疗潜力提供了参考。

研究人员表示，胎儿肝脏中的决定性造血作用支持造血干细胞和多能祖细胞（HSC / MPP）的自我更新和分化，但其在人类中的作用仍然不清楚。

附：英文原文

Title: Decoding human fetal liver haematopoiesis

Author: Dorin-Mirel Popescu, Rachel A. Botting, Emily Stephenson, Kile Green, Simone Webb, Laura Jardine, Emily F. Calderbank, Krzysztof Polanski, Issac Goh, Mirjana Efremova, Meghan Acres, Daniel Maunder, Peter Vegh, Yorick Gitton, Jong-Eun Park, Roser Vento-Tormo, Zhichao Miao, David Dixon, Rachel Rowell, David McDonald, James Fletcher, Elizabeth Poyner, Gary Reynolds, Michael Mather, Corina Moldovan, Lira Mamanova, Frankie Greig, Matthew D. Young, Kerstin B. Meyer, Steven Lisgo, Jaume Bacardit, Andrew Fuller, Ben Millar, Barbara Innes, Susan Lindsay, Michael J. T. Stubbington, Monika S. Kowalczyk, Bo Li, Orr Ashenberg, Marcin Tabaka, Danielle Dionne, Timothy L. Tickle, Michal Slyper, Orit Rozenblatt-Rosen, Andrew Filby, Peter Carey, Alexandra-Chloé Villani, Anindita Roy, Aviv Regev, Alain Chédotal, Irene Roberts, Berthold Göttgens, Sam Behjati, Elisa Laurenti, Sarah A. Teichmann & Muzlifah Haniffa 

Issue&Volume: 2019-10-09

Abstract: 

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells and multipotent progenitors (HSC/MPPs) but remains poorly defined in humans. Here, using single-cell transcriptome profiling of approximately 140,000 liver and 74,000 skin, kidney and yolk sac cells, we identify the repertoire of human blood and immune cells during development. We infer differentiation trajectories from HSC/MPPs and evaluate the influence of the tissue microenvironment on blood and immune cell development. We reveal physiological erythropoiesis in fetal skin and the presence of mast cells, natural killer and innate lymphoid cell precursors in the yolk sac. We demonstrate a shift in the haemopoietic composition of fetal liver during gestation away from being predominantly erythroid, accompanied by a parallel change in differentiation potential of HSC/MPPs, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a reference for harnessing the therapeutic potential of HSC/MPPs.

DOI: 10.1038/s41586-019-1652-y

Source:https://www.nature.com/articles/s41586-019-1652-y