1. Single-Cell RNA-Seq Mapping of Human Thymopoiesis Reveals Lineage Specification Trajectories and a Commitment Spectrum in T Cell Development
- Author
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Vi Luan Ha, Grigoriy Gogoshin, Andrei S. Rodin, Annie Luong, Sergio Branciamore, Jeong Eun Park, Virginia Camacho, Fan Li, Justin Le, Sweta B. Patel, Yong-Hwee Eddie Loh, Chintan Parekh, and Robert S. Welner
- Subjects
T-Lymphocytes ,T cell ,Immunology ,Priming (immunology) ,RNA-Seq ,Biology ,Article ,Immunophenotyping ,Mice ,Gene expression ,medicine ,Animals ,Humans ,Immunology and Allergy ,Cell Lineage ,Progenitor cell ,B cell ,Progenitor ,Thymocytes ,Gene Expression Profiling ,Lymphopoiesis ,Computational Biology ,Gene Expression Regulation, Developmental ,High-Throughput Nucleotide Sequencing ,RNA ,Cell Differentiation ,Cell biology ,Infectious Diseases ,medicine.anatomical_structure ,Single-Cell Analysis ,Transcriptome ,Biomarkers - Abstract
Summary 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.
- Published
- 2020
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