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Updated: Jun 19, 2025

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
Distinct epigenomic landscapes underlie tissue-specific memory T cell differentiation
Frank A Buquicchio1, Raissa Fonseca2, Patrick K Yan3
1Department 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.
Tissue-resident memory T (TRM) cells and circulating memory T (TCIRC) cells exhibit distinct epigenetic landscapes. This study reveals key regulators and epigenetic signatures defining TRM cell development and function across organs.
Area of Science:
- Immunology
- Epigenetics
- Cell Biology
Background:
- Memory CD8+ T cell pool comprises heterogeneous subsets with specialized functions.
- Understanding the epigenetic basis of tissue-resident memory T (TRM) cell heterogeneity is crucial.
Purpose of the Study:
- To investigate the epigenetic landscape of memory CD8+ T cells in various non-lymphoid organs and circulation.
- To identify regulators and epigenetic signatures of tissue-resident memory T (TRM) cell development.
- To compare epigenetic states of TRM cells, circulating memory T (TCIRC) cells, and exhausted T (TEX) cells.
Main Methods:
- Single-cell transposase-accessible chromatin sequencing (scATAC-seq) applied to CD8+ T cells from seven non-lymphoid organs and circulation.
- Analysis of epigenetic landscapes across four distinct infection models.
- Identification of transcriptional regulators and epigenetic signatures.
Main Results:
- Tissue-resident memory T (TRM) cells and circulating memory T (TCIRC) cells follow distinct epigenetic trajectories.
- Organ-specific transcriptional regulators (FOSB, FOS, FOSL1, BACH2) and a common TRM epigenetic signature were identified.
- Terminal exhausted T (TEX) cells possess unique epigenetic features distinct from TRM cells.
Conclusions:
- Epigenetic reprogramming drives the development of distinct tissue-adapted memory CD8+ T cell states.
- Chromatin accessibility changes are critical for defining TRM cell specialization and function.
- This study provides a comprehensive epigenetic resource for understanding memory T cell heterogeneity.
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