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Leaving no one behind: tracing every human thymocyte by single-cell RNA-sequencing

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Abstract

The thymus is the primary organ for T-cell development, providing an essential microenvironment consisting of the appropriate cytokine milieu and specialized stromal cells. Thymus-seeding progenitors from circulation immigrate into the thymus and undergo the stepwise T-cell specification, commitment, and selection processes. The transcriptional factors, epigenetic regulators, and signaling pathways involved in the T-cell development have been intensively studied using mouse models. Despite our growing knowledge of T-cell development, major questions remain unanswered regarding the ontogeny and early events of T-cell development at the fetal stage, especially in humans. The recently developed single-cell RNA-sequencing technique provides an ideal tool to investigate the heterogeneity of T-cell precursors and the molecular mechanisms underlying the divergent fates of certain T-cell precursors at the single-cell level. In this review, we aim to summarize the current progress of the study on human thymus organogenesis and thymocyte and thymic epithelial cell development, which is to shed new lights on developing novel strategies for in vitro T-cell regeneration and thymus rejuvenation.

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Acknowledgments

The authors apologize to peers whose work inspire this review but could not be cited due to the word limitation.

Funding

This work is supported by the Ministry of Science and Technology of China (the National Key Research and Development Program 2019YFA0110200 and 2016YFA0502203), the National Natural Science Foundation of China (82025002, 81871232 and 31870881), the 1.3.5 Project of disciplines of excellence and National Clinical Research Center for Geriatrics (Z20201001), and the West China Hospital, Sichuan University.

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  1. Yujun Deng and Hong Chen contributed equally to this work.

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  1. Department of Rheumatology and Immunology and State Key Laboratory of Biotherapy, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China

    Yujun Deng, Hong Chen, Keyue Wang, Huiyuan Zhang & Hongbo Hu

  2. State Key Laboratory of Experimental Hematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100071, China

    Yang Zeng

  3. State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, 100071, China

    Yang Zeng

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Deng, Y., Chen, H., Zeng, Y. et al. Leaving no one behind: tracing every human thymocyte by single-cell RNA-sequencing. Semin Immunopathol 43, 29–43 (2021). https://doi.org/10.1007/s00281-020-00834-9

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  • DOI: https://doi.org/10.1007/s00281-020-00834-9

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