Journal article

Distinct epigenomic landscapes underlie tissue-specific memory T cell differentiation

FA Buquicchio, R Fonseca, PK Yan, F Wang, M Evrard, A Obers, JC Gutierrez, CJ Raposo, JA Belk, B Daniel, P Zareie, KE Yost, Y Qi, Y Yin, KF Nico, FM Tierney, MR Howitt, CA Lareau, AT Satpathy, LK Mackay

Immunity | Published : 2024

Abstract

The memory CD8+ T cell pool contains phenotypically and transcriptionally heterogeneous subsets with specialized functions and recirculation patterns. Here, we examined the epigenetic landscape of CD8+ T cells isolated from seven non-lymphoid organs across four distinct infection models, alongside their circulating T cell counterparts. Using single-cell transposase-accessible chromatin sequencing (scATAC-seq), we found that tissue-resident memory T (TRM) cells and circulating memory T (TCIRC) cells develop along distinct epigenetic trajectories. We identified organ-specific transcriptional regulators of TRM cell development, including FOSB, FOS, FOSL1, and BACH2, and defined an epigenetic si..

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Grants

Awarded by Elmer and Sylvia Sramek Charitable Trust


Funding Acknowledgements

The authors thank the Flow Cytometry Unit and Bioresources Facility at Peter Doherty Institute (University of Melbourne) and the Stanford Functional Genomics Facility. This work was supported by Institutional Training Grant 5T32AI007290 (F.A.B.); ARC DECRA DE220100165 (R.F.); HHMI-Gates International Research Scholarship OPP1175796, NHMRC AP1113293, and Sylvia and Charles Viertel SMRF (L.K.M.); and NIH U01CA260852, the Parker Institute for Cancer Immunotherapy, a Lloyd J. Old STAR award from the Cancer Research Institute, a Career Award for Medical Scientists from the Burroughs Welcome Fund, a Pew-Stewart Scholars for Cancer Research Award, and a CRISPR Cures for Cancer Initiative Award (A.T.S.).r tute for Cancer Immunotherapy, a Lloyd J. Old STAR award from the Cancer Research Institute, a Career Award for Medical Scientists from the Burroughs Welcome Fund, a Pew-Stewart Scholars for Cancer Research Award, and a CRISPR Cures for Cancer Initiative Award (A.T.S.) .