Regeneration of humoral immunity from pluripotent stem cells by defined transcription factors
Regeneration of humoral immunity from pluripotent stem cells by defined transcription factors
SUMMARY Regeneration of humoral immunity from pluripotent stem cells (PSCs) is a crucial aim in translational medicine. However, reconstitution of complete, sustained, and functional B lymphopoiesis from PSCs has not yet been developed. Here, we successfully achieved regenerative B lymphopoiesis in B-cell deficient animals transplanted with PSC-derived hematopoietic progenitors (iHPCs) guided by synergistic expression of Runx1, Hoxa9, and Lhx2. Upon transplantation, the iHPCs immediately gave rise to pro/pre-B cells in recipients’ bone marrow, which were able to further differentiate into the entire B cell lineages, including innate B-1a, B-1b, MZ B cells, as well as adaptive FO B cells. In responding to antigen stimuli, the regenerative B cells produced adaptive humoral immune responses, sustained a prolonged antigen-specific antibody production, and formed immune-memory. Particularly, the regenerative B cells in spleen showed developing patterns of immunoglobulin chain-switch and hyper-mutation via a cross-talk with the host T follicular helper cells, which eventually formed T cell-dependent humoral responses. This study provides de novo evidence that B lymphopoiesis can be regenerated from PSCs via a HSC-independent approach, which provides insights into treating B-cell related humoral deficiencies using PSCs as unlimited cell resource.
Geng Yang、Lin Yunqing、Zhao Yalan、Du Juan、Hu Fangxiao、Wu Bingyan、Peng Huan、Liu Xiaofei、Wang Yao、Xia Chengxiang、Zhang Qi、Weng Qitong、Zhang Mengyun、Xiong Jiapin、Wang Jinyong、Liu Lijuan
CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)||Guangdong Provincial Key Laboratory of Stem cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)||Guangdong Provincial Key Laboratory of Stem cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesGMU-GIBH Joint School of Life Sciences, Guangzhou Medical UniversityCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)||Guangdong Provincial Key Laboratory of Stem cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)||Guangdong Provincial Key Laboratory of Stem cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||University of Chinese Academy of Sciences||Institute for stem cell and regeneration, Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)||Guangdong Provincial Key Laboratory of Stem cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||University of Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)||Guangdong Provincial Key Laboratory of Stem cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)||Guangdong Provincial Key Laboratory of Stem cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||University of Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)||Guangdong Provincial Key Laboratory of Stem cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)||Guangdong Provincial Key Laboratory of Stem cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||University of Chinese Academy of Sciences||Institute for stem cell and regeneration, Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)||Guangdong Provincial Key Laboratory of Stem cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||University of Chinese Academy of Sciences||Institute for stem cell and regeneration, Chinese Academy of SciencesGMU-GIBH Joint School of Life Sciences, Guangzhou Medical UniversityCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)||Guangdong Provincial Key Laboratory of Stem cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||University of Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)||Guangdong Provincial Key Laboratory of Stem cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||University of Chinese Academy of Sciences||Institute for stem cell and regeneration, Chinese Academy of SciencesCAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences||Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)||Guangdong Provincial Key Laboratory of Stem cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
基础医学生物科学研究方法、生物科学研究技术分子生物学
Runx1Hoxa9Lhx2pluripotent stem cellstranscription factorsregenerationB lymphopoiesisB-1 cellsB-2 cellshumoral immune response
Geng Yang,Lin Yunqing,Zhao Yalan,Du Juan,Hu Fangxiao,Wu Bingyan,Peng Huan,Liu Xiaofei,Wang Yao,Xia Chengxiang,Zhang Qi,Weng Qitong,Zhang Mengyun,Xiong Jiapin,Wang Jinyong,Liu Lijuan.Regeneration of humoral immunity from pluripotent stem cells by defined transcription factors[EB/OL].(2025-03-28)[2025-05-21].https://www.biorxiv.org/content/10.1101/2021.07.30.454442.点此复制
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