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

Immunity. 2020 Jun 16;52(6):1105-1118.e9. doi: 10.1016/j.immuni.2020.05.010.


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.

Keywords: T-lineage commitment; T-lineage specification; early thymic progenitors; human thymopoiesis; single-cell transcriptomes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Cell Differentiation / genetics*
  • Cell Lineage / genetics*
  • Computational Biology
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Immunophenotyping
  • Lymphopoiesis / genetics*
  • Mice
  • Single-Cell Analysis
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*
  • Thymocytes / cytology
  • Thymocytes / metabolism*
  • Transcriptome


  • Biomarkers