Immunity
Volume 48, Issue 6, 19 June 2018, Pages 1258-1270.e6
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A Single-Cell Transcriptomic Atlas of Thymus Organogenesis Resolves Cell Types and Developmental Maturation

https://doi.org/10.1016/j.immuni.2018.04.015Get rights and content
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Highlights

  • Single-cell RNA-seq reveals thymic cell types and developmental trajectories

  • Integration with GWASs links thymus development to autoimmune disorder etiologies

  • Machine learning measures organ culture maturation of lymphocytes and epithelium

  • Thymic epithelium develops normally despite exogenous retinoic acid

Summary

Thymus development is critical to the adaptive immune system, yet a comprehensive transcriptional framework capturing thymus organogenesis at single-cell resolution is still needed. We applied single-cell RNA sequencing (RNA-seq) to capture 8 days of thymus development, perturbations of T cell receptor rearrangement, and in vitro organ cultures, producing profiles of 24,279 cells. We resolved transcriptional heterogeneity of developing lymphocytes, and genetic perturbation confirmed T cell identity of conventional and non-conventional lymphocytes. We characterized maturation dynamics of thymic epithelial cells in vivo, classified cell maturation state in a thymic organ culture, and revealed the intrinsic capacity of thymic epithelium to preserve transcriptional regularity despite exposure to exogenous retinoic acid. Finally, by integrating the cell atlas with human genome-wide association study (GWAS) data and autoimmune-disease-related genes, we implicated embryonic thymus-resident cells as possible participants in autoimmune disease etiologies. This resource provides a single-cell transcriptional framework for biological discovery and molecular analysis of thymus organogenesis.

Keywords

thymus
single-cell RNA-seq
development
thymus organogenesis
transcriptomics
lymphocytes
cell atlas
thymic epithelium
lymphoid organ
Drop-seq

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2

These authors contributed equally

3

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