MSX2 suppression through inhibition of TGFβ signaling enhances hematopoietic differentiation of human embryonic stem cells
MSX2 suppression through inhibition of TGFβ signaling enhances hematopoietic differentiation of human embryonic stem cells
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通过抑制 TGFβ 信号传导抑制 MSX2 增强人胚胎干细胞的造血分化
DOI：
10.1186/s13287-020-01653-3
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发表时间：
2020-04
影响因子：
7.5
通讯作者：
Jiaxi Zhou
中科院分区：
文献类型：
--
作者：
Hongtao Wang;Mengge Wang;Yu Wang;Yuqi Wen;Xiaoyuan Chen;Dan Wu;Pei Su;Wen Zhou;Lihong Shi;Jiaxi Zhou
由于缺乏对造血发育的全面理解，从人类多能干细胞（hPSCs）生成功能性血细胞的策略在很大程度上仍然是不成功的。内皮-造血转化（EHT）是造血发生的关键机制，受TGF-β信号负调控。然而，对于EHT过程中TGF-β信号传导的潜在细节知之甚少。方法在本研究中，通过全基因组基因分析，我们发现肌肉节段同源box2 （MSX2）是EHT期间TGF-β信号传导的潜在介质。我们利用CRISPR/Cas9技术生成了msx2缺失的人胚胎干细胞（hESC）系，并诱导其进行造血分化。研究了MSX2在EHT中造血和tgf - β信号功能调控中的作用。结果我们发现MSX2是一种新的人造血调节因子。MSX2缺失促进hESCs产生造血细胞。功能和生物信息学研究进一步表明，MSX2缺失通过促进EHT增强hESCs的造血分化。从机制上讲，MSX2作为tgf - β信号的下游靶点，介导其在EHT中的功能。结论sour的结果不仅提高了对EHT的理解，而且可能为从人乳头状细胞中高效产生功能性血细胞用于再生医学提供新的见解。
BackgroundStrategies of generating functional blood cells from human pluripotent stem cells (hPSCs) remain largely unsuccessful due to the lack of a comprehensive understanding of hematopoietic development. Endothelial-to-hematopoietic transition (EHT) serves as the pivotal mechanism for the onset of hematopoiesis and is negatively regulated by TGF-β signaling. However, little is known about the underlying details of TGF-β signaling during EHT.MethodsIn this study, by applying genome-wide gene profiling, we identified muscle segment homeobox2 (MSX2) as a potential mediator of TGF-β signaling during EHT. We generated MSX2-deleted human embryonic stem cell (hESC) lines using the CRISPR/Cas9 technology and induced them to undergo hematopoietic differentiation. The role of MSX2 in hematopoiesis and functional regulation of TGFβ signaling in EHT was studied.ResultsWe identified MSX2 as a novel regulator of human hematopoiesis. MSX2 deletion promotes the production of hematopoietic cells from hESCs. Functional and bioinformatics studies further demonstrated that MSX2 deletion augments hematopoietic differentiation of hESCs by facilitating EHT. Mechanistically, MSX2 acts as a downstream target of TGFβ signaling to mediate its function during EHT.ConclusionsOur results not only improve the understanding of EHT, but may also provide novel insight into the efficient production of functional blood cells from hPSCs for regenerative medicine.
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影响因子：
5.3
作者：
通讯作者：
--
MSX2 通过调节 TWIST1 和 PRAME 启动并加速 hPSC 的间充质干细胞/基质细胞规范
影响因子：
5.9
作者：
Zhang L;Wang H;Liu C;Wu Q;Su P;Wu D;Guo J;Zhou W;Xu Y;Shi L;Zhou J
通讯作者：
Zhou J
影响因子：
2.9
作者：
Elizabeth P. Newberry;T. Latifi;John T. Battaile;D. Towler
通讯作者：
Elizabeth P. Newberry;T. Latifi;John T. Battaile;D. Towler
MSX2 通过同时抑制 SOX2 和激活 NODAL 信号传导介导人多能干细胞进入中内胚层
影响因子：
44.1
作者：
Wu, Qingqing;Zhang, Leisheng;Zhou, Jiaxi
通讯作者：
Zhou, Jiaxi
影响因子：
20.3
作者：
Zambidis, ET;Peault, B;Civin, CI
通讯作者：
Civin, CI