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Distinct epigenomic landscapes underlie tissue-specific memory T cell differentiation.
Buquicchio, Frank A; Fonseca, Raissa; Yan, Patrick K; Wang, Fangyi; Evrard, Maximilien; Obers, Andreas; Gutierrez, Jacob C; Raposo, Colin J; Belk, Julia A; Daniel, Bence; Zareie, Pirooz; Yost, Kathryn E; Qi, Yanyan; Yin, Yajie; Nico, Katherine F; Tierney, Flora M; Howitt, Michael R; Lareau, Caleb A; Satpathy, Ansuman T; Mackay, Laura K.
Afiliação
  • Buquicchio FA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA.
  • Fonseca R; Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Yan PK; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA.
  • Wang F; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA.
  • Evrard M; Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Obers A; Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Gutierrez JC; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA.
  • Raposo CJ; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA.
  • Belk JA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
  • Daniel B; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Zareie P; Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Yost KE; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Qi Y; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Yin Y; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA.
  • Nico KF; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA.
  • Tierney FM; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA.
  • Howitt MR; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA.
  • Lareau CA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA; Parker Institute for Cancer Immunotherapy, Stanford University, Stanford, CA 94129, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158
  • Satpathy AT; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Program in Immunology, Stanford University, Stanford, CA 94304, USA; Parker Institute for Cancer Immunotherapy, Stanford University, Stanford, CA 94129, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158
  • Mackay LK; Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia. Electronic address: lkmackay@unimelb.edu.au.
Immunity ; 2024 Jul 16.
Article em En | MEDLINE | ID: mdl-39043184
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 signature common to TRM cells across organs. Finally, we found that although terminal TEX cells share accessible regulatory elements with TRM cells, they are defined by TEX-specific epigenetic features absent from TRM cells. Together, this comprehensive data resource shows that TRM cell development is accompanied by dynamic transcriptome alterations and chromatin accessibility changes that direct tissue-adapted and functionally distinct T cell states.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article