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...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.展开更多
目的：明确LHX-2在角膜干细胞中的表达。方法：取20∽35岁青年人角膜中央区域和边缘区域上皮组织。提取RNA和蛋白行Real time PCR和Western Blot,检测LHX-2在角膜缘和中央RNA及蛋白水平的差异。结果：人角膜缘上皮LHX-2的m RNA和蛋白水...目的：明确LHX-2在角膜干细胞中的表达。方法：取20∽35岁青年人角膜中央区域和边缘区域上皮组织。提取RNA和蛋白行Real time PCR和Western Blot,检测LHX-2在角膜缘和中央RNA及蛋白水平的差异。结果：人角膜缘上皮LHX-2的m RNA和蛋白水平均高于角膜中央,两组比较,差异具有统计学意义（P〈0.05）。结论：LHχ2可能成为一种新的角膜缘上皮干细胞的分子标志,为角膜缘上皮干细胞的鉴定和分化提供新的方向。展开更多
基金This work was supported by the National Key R&D Program of China(2019YFA0110203,2020YFA0112404)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010601)+4 种基金the Frontier Science Research Program of the CAS(QYZDB-SSW-SMC057)the Key R&D Program of Guangdong Province(2020B1111470001)the National Natural Science Foundation of China(81925002)the Key Research&Development Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory(2018GZR110104006)the Science and Technology Planning Project of Guangdong Province,China(2020B1212060052).
文摘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.
文摘目的：明确LHX-2在角膜干细胞中的表达。方法：取20∽35岁青年人角膜中央区域和边缘区域上皮组织。提取RNA和蛋白行Real time PCR和Western Blot,检测LHX-2在角膜缘和中央RNA及蛋白水平的差异。结果：人角膜缘上皮LHX-2的m RNA和蛋白水平均高于角膜中央,两组比较,差异具有统计学意义（P〈0.05）。结论：LHχ2可能成为一种新的角膜缘上皮干细胞的分子标志,为角膜缘上皮干细胞的鉴定和分化提供新的方向。
