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Immunity. 2018 Jun 19;48(6):1258-1270.e6. doi: 10.1016/j.immuni.2018.04.015. Epub 2018 Jun 5.

A Single-Cell Transcriptomic Atlas of Thymus Organogenesis Resolves Cell Types and Developmental Maturation.

Author information

1
Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA 01605, USA.
2
Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: rene.maehr@umassmed.edu.

Abstract

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:

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

PMID:
29884461
PMCID:
PMC6013397
[Available on 2019-06-19]
DOI:
10.1016/j.immuni.2018.04.015
[Indexed for MEDLINE]

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