Chromatin landscape alteration uncovers multiple transcriptional circuits during memory CD8+ T-cell differentiation
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.
Authors
- Bo Zhu (ORCID: https://orcid.org/0000-0002-5829-9581)
- Zhengliang Yue
- Lifan Xu
- Dan Xiong (ORCID: https://orcid.org/0000-0001-8660-9228)
- Xingxing Su
- Luming Xu (ORCID: https://orcid.org/0000-0002-3746-1332)
- Shun� Lei
- Lilin Ye (ORCID: https://orcid.org/0000-0003-0778-3311)
- Qiao Liu (ORCID: https://orcid.org/0000-0003-3224-2672)
- Zhonghui Tang (ORCID: https://orcid.org/0000-0003-2907-3986)
- Jianjun Hu (ORCID: https://orcid.org/0000-0002-5177-399X)
- Xiangyu Chen (ORCID: https://orcid.org/0000-0001-7947-3211)
- Xia Wu (ORCID: https://orcid.org/0009-0002-2584-1765)
- Yan Zhang (ORCID: https://orcid.org/0000-0001-7039-9780)
- Lisha Wang
- Rong Liu (ORCID: https://orcid.org/0000-0001-7477-6520)
- Yongchang Chen (ORCID: https://orcid.org/0000-0002-0678-9247)
- Qizhao Huang
- Ziying Xie
- Wei Dong (ORCID: https://orcid.org/0009-0005-3616-516X)
- Yingjiao Cao (ORCID: https://orcid.org/0000-0003-1689-0397)
- Ling Ran (ORCID: https://orcid.org/0009-0007-8097-0857)
- Shuqiong Wen
- Chenxi Qin
Institutions
- Army Medical University (CN)
- Sun Yat-sen University (CN)
- Xinqiao Hospital (CN)
- Stomatological Hospital of Chongqing Medical University (CN)
- The First Affiliated Hospital, Sun Yat-sen University (CN)
- Southwest Hospital (CN)
- Institute of Immunology (HR)
- Immune Regulation (United Kingdom) (GB)
- Children's Hospital of Chongqing Medical University (CN)
- Southern Medical University (CN)
- Chongqing Medical University (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Protein & Cell
- Published
- 2025-01-09
- DOI
- https://doi.org/10.1093/procel/pwaf003
- Citations
- 1
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 0.80
Funders
- National Science Foundation
- Chongqing Postdoctoral Science Foundation
- National Natural Science Foundation of China