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单细胞多组学发现新型淋巴活化祖细胞
作者：小柯机器人 发布时间：2020/10/22 14:45:11

澳大利亚沃尔特与伊丽莎·霍尔医学研究所Shalin H. Naik团队利用单细胞多组学发现一种以Dach1下调为标志的新淋巴活化祖细胞。相关论文于2020年10月19日在线发表在《自然—免疫学》杂志上。

据研究人员介绍，血细胞发育的经典观点是，多能造血干细胞和祖细胞（HSPC）在定义的阶段出现谱系限制。Lin-c-Kit+Sca-1+Flt3+细胞，称为淋巴活化的多能祖细胞（LMPP），其失去了巨核细胞和红系细胞的潜能，但命运却不尽相同。
 
通过单细胞RNA测序，研究人员确定Dach1及其相关基因在这一部分中的表达与髓质/干基因共表达，但与淋巴样基因呈负相关。通过生成Dach1-GFP报告基因小鼠，研究人员确定了LMPP中转录和功能独特的Dach1-GFP-亚群，其淋巴潜能低至可忽略的经典髓样潜能。 研究人员将这些称为“淋巴源性祖细胞”（LPP）。
 
这些发现定义了造血过程中淋巴样发育的早期定性分支点，也是LPP分离的新手段。
 
附：英文原文

Title: A new lymphoid-primed progenitor marked by Dach1 downregulation identified with single cell multi-omics

Author: Daniela Amann-Zalcenstein, Luyi Tian, Jaring Schreuder, Sara Tomei, Dawn S. Lin, Kirsten A. Fairfax, Jessica E. Bolden, Mark D. McKenzie, Andrew Jarratt, Adrienne Hilton, Jacob T. Jackson, Ladina Di Rago, Matthew P. McCormack, Carolyn A. de Graaf, Olivia Stonehouse, Samir Taoudi, Warren S. Alexander, Stephen L. Nutt, Matthew E. Ritchie, Ashley P. Ng, Shalin H. Naik

Issue&Volume: 2020-10-19

Abstract: A classical view of blood cell development is that multipotent hematopoietic stem and progenitor cells (HSPCs) become lineage-restricted at defined stages. Linc-Kit+Sca-1+Flt3+ cells, termed lymphoid-primed multipotent progenitors (LMPPs), have lost megakaryocyte and erythroid potential but are heterogeneous in their fate. Here, through single-cell RNA sequencing, we identify the expression of Dach1 and associated genes in this fraction as being coexpressed with myeloid/stem genes but inversely correlated with lymphoid genes. Through generation of Dach1–GFP reporter mice, we identify a transcriptionally and functionally unique Dach1–GFP subpopulation within LMPPs with lymphoid potential with low to negligible classic myeloid potential. We term these ‘lymphoid-primed progenitors’ (LPPs). These findings define an early definitive branch point of lymphoid development in hematopoiesis and a means for prospective isolation of LPPs.

DOI: 10.1038/s41590-020-0799-x

Source: https://www.nature.com/articles/s41590-020-0799-x

期刊信息

Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：23.53
官方网址：https://www.nature.com/ni/
投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex