Chromatin landscape alteration uncovers multiple transcriptional circuits during memory CD8+ T-cell differentiation.

Qiao LIU; Wei DONG; Rong LIU; Luming XU; Ling RAN; Ziying XIE; Shun LEI; Xingxing SU; Zhengliang YUE; Dan XIONG; Lisha WANG; Shuqiong WEN; Yan ZHANG; Jianjun HU; Chenxi QIN; Yongchang CHEN; Bo ZHU; Xiangyu CHEN; Xia WU; Lifan XU; Qizhao HUANG; Yingjiao CAO; Lilin YE; Zhonghui TANG

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Chromatin landscape alteration uncovers multiple transcriptional circuits during memory CD8+ T-cell differentiation.

Author: Qiao LIU ¹ ; Wei DONG ² ; Rong LIU ² ; Luming XU ³ ; Ling RAN ⁴ ; Ziying XIE ² ; Shun LEI ⁴ ; Xingxing SU ⁴ ; Zhengliang YUE ⁴ ; Dan XIONG ² ; Lisha WANG ⁴ ; Shuqiong WEN ⁵ ; Yan ZHANG ⁶ ; Jianjun HU ⁷ ; Chenxi QIN ⁴ ; Yongchang CHEN ⁸ ; Bo ZHU ⁸ ; Xiangyu CHEN ⁶ ; Xia WU ² ; Lifan XU ⁴ ; Qizhao HUANG ⁶ ; Yingjiao CAO ³ ; Lilin YE ⁴ ; Zhonghui TANG ²
Author Information

1. Department of Hematology and Oncology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing 400014, China.
2. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
3. Guangdong Province Key Laboratory of Immune Regulation and Immunotherapy, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China.
4. Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
5. Stomatological Hospital of Chongqing Medical University, Chongqing 400015, China.
6. Institute of Immunological Innovation and Translation, Chongqing Medical University, Chongqing 400016, China.
7. Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
8. Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 214426, China.
Publication Type:Journal Article
Keywords: T cell; chromatin; epigenome; interactions; memory
MeSH: CD8-Positive T-Lymphocytes/metabolism*; Cell Differentiation; Chromatin/immunology*; Animals; Mice; Immunologic Memory; Epigenesis, Genetic; SOXC Transcription Factors/immunology*; NF-E2-Related Factor 2/immunology*; Mice, Inbred C57BL; Gene Regulatory Networks; Enhancer Elements, Genetic
From: Protein & Cell 2025;16(7):575-601
CountryChina
Language:English
Abstract: Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.