4.6 Article

Integrative Single-Cell Transcriptomic Analysis of Human Fetal Thymocyte Development

期刊

FRONTIERS IN GENETICS
卷 12, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fgene.2021.679616

关键词

fetal thymus; human and murine; single-cell RNA-seq; T lymphopoiesis; transcriptional dynamics

资金

  1. National Key R&D Program of China [2018YFC1004500, 2017YFC1001303]
  2. National Natural Science Foundation of China [81671456, 81801409]
  3. Chinese Academy of Medical Sciences Research Unit [2019RU056]
  4. International Cooperation Project of China
  5. Canada NSFC [81661128010]
  6. CAMS Innovation Fund for Medical Sciences [2019-I2M-5-064]
  7. Shanghai Sailing Program [18YF1424700]

向作者/读者索取更多资源

The study conducted integrative single-cell analyses of thymocytes at different gestational ages, identifying candidate genes regulating T cell receptor lineage selection and characterizing the trajectory of early thymocyte commitment during fetal growth. Comparisons with mouse data revealed both conserved and species-specific transcriptional dynamics, as well as susceptibility genes associated with autoimmune disorders.
Intrathymic differentiation of T lymphocytes begins as early as intrauterine stage, yet the T cell lineage decisions of human fetal thymocytes at different gestational ages are not currently understood. Here, we performed integrative single-cell analyses of thymocytes across gestational ages. We identified conserved candidates underlying the selection of T cell receptor (TCR) lineages in different human fetal stages. The trajectory of early thymocyte commitment during fetal growth was also characterized. Comparisons with mouse data revealed conserved and species-specific transcriptional dynamics of thymocyte proliferation, apoptosis and selection. Genome-wide association study (GWAS) data associated with multiple autoimmune disorders were analyzed to characterize susceptibility genes that are highly expressed at specific stages during fetal thymocyte development. In summary, our integrative map describes previously underappreciated aspects of human thymocyte development, and provides a comprehensive reference for understanding T cell lymphopoiesis in a self-tolerant and functional adaptive immune system.

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