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Single-Cell RNA-Seq Mapping of Human Thymopoiesis Reveals Lineage Specification Trajectories and a Commitment Spectrum in T Cell Development.
Immunity ( IF 25.5 ) Pub Date : 2020-06-16 , DOI: 10.1016/j.immuni.2020.05.010
Justin Le 1 , Jeong Eun Park 1 , Vi Luan Ha 1 , Annie Luong 1 , Sergio Branciamore 2 , Andrei S Rodin 2 , Grigoriy Gogoshin 2 , Fan Li 1 , Yong-Hwee Eddie Loh 3 , Virginia Camacho 4 , Sweta B Patel 4 , Robert S Welner 4 , Chintan Parekh 5
Affiliation  

The challenges in recapitulating in vivo human T cell development in laboratory models have posed a barrier to understanding human thymopoiesis. Here, we used single-cell RNA sequencing (sRNA-seq) to interrogate the 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 states characterized by multilineage priming followed by gradual T cell commitment. The earliest progenitors in the differentiation trajectory were CD7 and expressed a stem-cell-like transcriptional profile, but had also initiated T cell priming. Clustering analysis identified a CD34+ subpopulation primed for the plasmacytoid dendritic lineage, suggesting an intrathymic dendritic specification pathway. CD2 expression defined T cell commitment stages where loss of B cell potential preceded that of myeloid potential. These datasets delineate gene expression profiles spanning key differentiation events in human thymopoiesis and provide a resource for the further study of human T cell development.



中文翻译:

人胸腺单细胞RNA序列映射揭示了沿袭规范轨迹和T细胞发育中的承诺谱。

在实验室模型中概括体内人类T细胞发育的挑战,已成为理解人类胸腺生成的障碍。在这里,我们使用单细胞RNA测序(的sRNA-SEQ)询问所述稀有CD34 +祖细胞和更分化的CD34 -在人出生后胸腺馏分。CD34 +胸腺祖细胞由一系列规格和定性状态组成,其特征是多谱系引物继之以逐步的T细胞定型。在分化轨迹最早的祖细胞CD7 -和表达的干细胞样转录谱,而且还发起了T细胞引发。聚类分析确定了CD34 +亚群为浆细胞样树突状谱系致敏,提示胸腺内树突状规范途径。CD2表达定义了T细胞定型阶段,其中B细胞电位的丧失先于骨髓电位的丧失。这些数据集描绘了跨越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。

更新日期:2020-06-16
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