Transcriptional Basis of Mouse and Human Dendritic Cell Heterogeneity

Chrysothemis C. Brown, Herman Gudjonson, Yuri Pritykin, Deeksha Deep, Vincent Philippe Lavallée, Alejandra Mendoza, Rachel Fromme, Linas Mazutis, Charlotte Ariyan, Christina Leslie, Dana Pe'er, Alexander Y. Rudensky

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Dendritic cells (DCs) play a critical role in orchestrating adaptive immune responses due to their unique ability to initiate T cell responses and direct their differentiation into effector lineages. Classical DCs have been divided into two subsets, cDC1 and cDC2, based on phenotypic markers and their distinct abilities to prime CD8 and CD4 T cells. While the transcriptional regulation of the cDC1 subset has been well characterized, cDC2 development and function remain poorly understood. By combining transcriptional and chromatin analyses with genetic reporter expression, we identified two principal cDC2 lineages defined by distinct developmental pathways and transcriptional regulators, including T-bet and RORγt, two key transcription factors known to define innate and adaptive lymphocyte subsets. These novel cDC2 lineages were characterized by distinct metabolic and functional programs. Extending our findings to humans revealed conserved DC heterogeneity and the presence of the newly defined cDC2 subsets in human cancer.

Original languageEnglish (US)
Pages (from-to)846-863.e24
JournalCell
Volume179
Issue number4
DOIs
StatePublished - Oct 31 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Keywords

  • ATAC-sequencing
  • T-bet
  • dendritic cells
  • myeloid cells
  • single-cell RNA-sequencing
  • transcriptional regulation

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