Author
Listed:
- Yuechen Luo
(Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)
- Changlu Xu
(Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)
- Bing Wang
(Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)
- Qing Niu
(Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)
- Xiuhua Su
(Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)
- Yingnan Bai
(Novogene Co., Ltd.)
- Shuxian Zhu
(Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)
- Chunxiao Zhao
(Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)
- Yunyan Sun
(Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)
- Jiali Wang
(Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)
- Maolan Liu
(Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)
- Xiaolei Sun
(Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)
- Ge Song
(Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)
- Haidong Cui
(Hangzhou First People’s Hospital)
- Xiaoli Chen
(the Affiliated Ganzhou Hospital of Nanchang University)
- Huifang Huang
(Fujian Medical University Union Hospital)
- Haikun Wang
(Institut Pasteur of Shanghai, Chinese Academy of Sciences)
- Mingzhe Han
(Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)
- Erlie Jiang
(Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)
- Lihong Shi
(Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College)
- Xiaoming Feng
(Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Fujian Medical University Union Hospital)
Abstract
Human FOXP3+ regulatory T (Treg) cells are central to immune tolerance. However, their heterogeneity and differentiation remain incompletely understood. Here we use single-cell RNA and T cell receptor sequencing to resolve Treg cells from healthy individuals and patients with or without acute graft-versus-host disease (aGVHD) who undergo stem cell transplantation. These analyses, combined with functional assays, separate Treg cells into naïve, activated, and effector stages, and resolve the HLA-DRhi, LIMS1hi, highly suppressive FOXP3hi, and highly proliferative MKI67hi effector subsets. Trajectory analysis assembles Treg subsets into two differentiation paths (I/II) with distinctive phenotypic and functional programs, ending with the FOXP3hi and MKI67hi subsets, respectively. Transcription factors FOXP3 and SUB1 contribute to some Path I and Path II phenotypes, respectively. These FOXP3hi and MKI67hi subsets and two differentiation pathways are conserved in transplanted patients, despite having functional and migratory impairments under aGVHD. These findings expand the understanding of Treg cell heterogeneity and differentiation and provide a single-cell atlas for the dissection of Treg complexity in health and disease.
Suggested Citation
Yuechen Luo & Changlu Xu & Bing Wang & Qing Niu & Xiuhua Su & Yingnan Bai & Shuxian Zhu & Chunxiao Zhao & Yunyan Sun & Jiali Wang & Maolan Liu & Xiaolei Sun & Ge Song & Haidong Cui & Xiaoli Chen & Hui, 2021.
"Single-cell transcriptomic analysis reveals disparate effector differentiation pathways in human Treg compartment,"
Nature Communications, Nature, vol. 12(1), pages 1-14, December.
Handle:
RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24213-6
DOI: 10.1038/s41467-021-24213-6
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