轉(zhuǎn)錄因子誘導(dǎo)多能干細(xì)胞再生免疫活性B淋巴細(xì)胞

2021年11月，中國科學(xué)院廣州生物醫(yī)藥與健康研究所；中國科學(xué)院再生生物學(xué)重點實驗室；中國科學(xué)院廣州生物醫(yī)藥與衛(wèi)生研究院；廣東省干細(xì)胞與再生醫(yī)學(xué)重點實驗室；中國科學(xué)院大學(xué)；中國科學(xué)院干細(xì)胞與再生研究所；廣州醫(yī)學(xué)院；GMU-GIBH生命科學(xué)聯(lián)合學(xué)院(CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China；Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China；Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China；University of Chinese Academy of Sciences, Beijing 100049, China；Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China；GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, China.) Jinyong Wang老師研究團(tuán)隊在《Cellular & Molecular Immunology》上發(fā)表論文：

“Regeneration of immunocompetent B lymphopoiesis from pluripotent stem cells guided by transcription factors”

“轉(zhuǎn)錄因子誘導(dǎo)多能干細(xì)胞再生免疫活性B淋巴細(xì)胞”

Abstract：

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.

摘要：

從多能干細(xì)胞(PSCs)中再生功能性B淋巴細(xì)胞是具有挑戰(zhàn)性的，目前還沒有可靠的方法。在這里，我們揭示了三個關(guān)鍵因子Lhx2、Hoxa9和Runx1的指導(dǎo)作用，它們的同時表達(dá)優(yōu)先驅(qū)動B譜系命運承諾和以PSCs為細(xì)胞源的體內(nèi)B淋巴生成。在Lhx2、Hoxa9和Runx1表達(dá)的情況下，psc衍生的誘導(dǎo)造血祖細(xì)胞(iHPCs)立即在受體骨髓中產(chǎn)生pro/pre-B細(xì)胞，這些細(xì)胞能夠進(jìn)一步分化成完整的B細(xì)胞系，包括先天B-1a、B-1b和邊緣區(qū)B細(xì)胞，以及適應(yīng)性濾泡B細(xì)胞。特別是，再生B細(xì)胞產(chǎn)生適應(yīng)性體液免疫反應(yīng)，持續(xù)產(chǎn)生抗原特異性抗體，并在抗原挑戰(zhàn)下形成免疫記憶。再生B細(xì)胞通過與宿主T濾泡輔助細(xì)胞的串?dāng)_，表現(xiàn)出免疫球蛋白鏈切換和超突變的自然B細(xì)胞發(fā)育模式，最終形成T細(xì)胞依賴性體液反應(yīng)。這項研究提供了新的證據(jù)，證明通過hsc獨立的方法可以從psc再生B淋巴系統(tǒng)，這為利用psc作為無限的細(xì)胞資源治療B細(xì)胞相關(guān)缺陷提供了見解。

該論文中，OP9-DL1細(xì)胞(GFP+)的體外培養(yǎng)是使用Ausbian特級胎牛血清完成的。欲了解或購買Ausbian特級胎牛血清可以聯(lián)系北京締一生物400-166-8600.