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单细胞测序揭示T细胞发育过程中的分化轨迹
2020-06-17 22:45

美国洛杉矶儿童医院Chintan Parekh研究小组利用人类胸腺单细胞RNA测序,揭示出T细胞发育过程中的分化轨迹。该研究于2020年6月16日发表于《免疫》。

研究人员使用单细胞RNA测序(sRNA-seq)来检测了人出生后胸腺中稀有的CD34+祖细胞和分化程度更高的CD34-组分。CD34+胸腺祖细胞由一系列分化和确定状态组成,其特征是多谱系活化以及随后的T细胞定型。分化轨迹中最早的祖细胞是CD7-,并表达了干细胞样的转录特征,但也起始了T细胞的活化。
 
聚类分析确定了浆细胞样树突状谱系引发的CD34+亚群,这提示了胸腺内树突状的分化途径。CD2表达定义了T细胞定型阶段,其中B细胞潜能的丧失先于髓系潜能的丧失。
 
这些数据集描绘了人类胸腺生成过程中关键分化事件的基因表达谱,并为进一步研究人类T细胞发育提供了资源。
 
据悉,在实验室模型中模拟体内人类T细胞发育是了解人类胸腺生成的主要障碍。

Title: Single-Cell RNA-Seq Mapping of Human Thymopoiesis Reveals Lineage Specification Trajectories and a Commitment Spectrum in T Cell Development

Author: Justin Le, Jeong Eun Park, Vi Luan Ha, Annie Luong, Sergio Branciamore, Andrei S. Rodin, Grigoriy Gogoshin, Fan Li, Yong-Hwee Eddie Loh, Virginia Camacho, Sweta B. Patel, Robert S. Welner, Chintan Parekh

Issue&Volume: 2020/06/16

Abstract: The challenges in recapitulating in vivo human T cell development in laboratory models have posed a barrier to understandinghuman thymopoiesis. Here, we used single-cell RNA sequencing (sRNA-seq) to interrogatethe rare CD34+ progenitor and the more differentiated CD34– fractions in the human postnatal thymus. CD34+ thymic progenitors were comprised of a spectrum of specification and commitment statescharacterized by multilineage priming followed by gradual T cell commitment. The earliestprogenitors in the differentiation trajectory were CD7– and expressed a stem-cell-like transcriptional profile, but had also initiated T cellpriming. Clustering analysis identified a CD34+ subpopulation primed for the plasmacytoid dendritic lineage, suggesting an intrathymicdendritic specification pathway. CD2 expression defined T cell commitment stages whereloss of B cell potential preceded that of myeloid potential. These datasets delineategene expression profiles spanning key differentiation events in human thymopoiesisand provide a resource for the further study of human T cell development.

DOI: 10.1016/j.immuni.2020.05.010

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30218-1

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:43.474
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx


本期文章:《免疫》:Online/在线发表

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