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中文論文題目: Regeneration of immunocompetent B lymphopoiesis from pluripotent stem cells guided by transcription factors
英文論文題目: Regeneration of immunocompetent B lymphopoiesis from pluripotent stem cells guided by transcription factors
作者: Qi Zhang, Bingyan Wu, Qitong Weng, Fangxiao Hu, Yunqing Lin, Chengxiang Xia, Huan Peng,Yao Wang, Xiaofei Liu, Lijuan Liu, Jiapin Xiong, Yang Geng, Yalan Zhao, Mengyun Zhang, Juan Du and Jinyong Wang
論文出處:
刊物名稱: Cellular & Molecular Immunology
年: 2022
卷: 19
期: 4
頁: 492-503
聯係作者: Jinyong Wang
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影響因子: 22.100
摘要: Regeneration of functional B lymphopoiesis from pluripotent stem cells (PSCs) is challenging, and reliable methods have not been developed. Here, we unveiled the guiding role of three essential factors, Lhx2, Hoxa9, and Runx1, the simultaneous expression of which preferentially drives B lineage fate commitment and in vivo B lymphopoiesis using PSCs as a cell source. In the presence of Lhx2, Hoxa9, and Runx1 expression, PSC-derived induced hematopoietic progenitors (iHPCs) immediately gave rise to pro/pre-B cells in recipient bone marrow, which were able to further differentiate into entire B cell lineages, including innate B-1a, B-1b, and marginal zone B cells, as well as adaptive follicular B cells. In particular, the regenerative B cells produced adaptive humoral immune responses, sustained antigen-specific antibody production, and formed immune memory in response to antigen challenges. The regenerative B cells showed natural B cell development patterns of immunoglobulin chain switching and hypermutation via cross-talk with host T follicular helper cells, which eventually formed T cell-dependent humoral responses. This study exhibits de novo evidence that B lymphopoiesis can be regenerated from PSCs via an HSC-independent approach, which provides insights into treating B cell-related deficiencies using PSCs as an unlimited cell resource.
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