MSX2 Initiates and Accelerates Mesenchymal Stem/Stromal Cell Specification of hPSCs by Regulating TWIST1 and PRAME.
MSX2 Initiates and Accelerates Mesenchymal Stem/Stromal Cell Specification of hPSCs by Regulating TWIST1 and PRAME.
复制标题
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
DOI：
10.1016/j.stemcr.2018.06.019
复制
发表时间：
2018-08-14
影响因子：
5.9
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Zhang L;Wang H;Liu C;Wu Q;Su P;Wu D;Guo J;Zhou W;Xu Y;Shi L;Zhou J
人多能干细胞（hPSC）分化为间充质细胞谱系的分子机制的知识上的差距阻碍了hPSC用于基于细胞的治疗的应用。在这项研究中，我们确定了肌肉节段同源框2（MSX 2）在启动和加速导致hPSC向间充质干细胞/基质细胞（MSC）分化的分子程序中的关键作用。MSX 2的遗传缺失损害hPSC向MSC的分化。当辅助可溶性分子的混合物时，MSX 2异位表达诱导hPSC形成几乎同质且功能齐全的MSC。在机制上，MSX 2诱导hPSC形成神经嵴细胞，这是MSC之前的中间细胞阶段，并通过调节TWIST 1和PRAME进一步分化。此外，我们发现MSX 2也是hPSC通过中内胚层和滋养层分化为MSC所必需的。我们的研究结果为hPSC向MSC的谱系特化提供了新的机制见解，并为干细胞在再生医学中的应用提供了有效的策略。MSX 2通过靶向TWIST 1和PRAME调节间充质细胞的发生。在这篇文章中，Zhou及其同事表明，MSX 2通过调节TWIST 1和PRAME快速启动和加速MSC向hPSC的特化。该研究为hPSC向MSC的谱系特化提供了新的机制见解，并为干细胞在再生医学中的应用提供了有效的策略。
The gap in knowledge of the molecular mechanisms underlying differentiation of human pluripotent stem cells (hPSCs) into the mesenchymal cell lineages hinders the application of hPSCs for cell-based therapy. In this study, we identified a critical role of muscle segment homeobox 2 (MSX2) in initiating and accelerating the molecular program that leads to mesenchymal stem/stromal cell (MSC) differentiation from hPSCs. Genetic deletion of MSX2 impairs hPSC differentiation into MSCs. When aided with a cocktail of soluble molecules, MSX2 ectopic expression induces hPSCs to form nearly homogeneous and fully functional MSCs. Mechanistically, MSX2 induces hPSCs to form neural crest cells, an intermediate cell stage preceding MSCs, and further differentiation by regulating TWIST1 and PRAME. Furthermore, we found that MSX2 is also required for hPSC differentiation into MSCs through mesendoderm and trophoblast. Our findings provide novel mechanistic insights into lineage specification of hPSCs to MSCs and effective strategies for applications of stem cells for regenerative medicine. MSX2 rapidly initiates mesenchymal program in hPSCs Functional MSCs are derived with MSX2 programming and soluble factors Neural crest is the intermediate stage from hPSCs to MSCs with MSX2 programming MSX2 regulates mesengenesis by targeting TWIST1 and PRAME In this article, Zhou and colleagues show that MSX2 rapidly initiates and accelerates MSC specification of hPSCs by regulating TWIST1 and PRAME. The study provides novel mechanistic insights into lineage specification of hPSCs to MSCs and effective strategies for applications of stem cells for regenerative medicine.
登录
查看更多内容
影响因子：
6
作者：
Gibson JD;O'Sullivan MB;Alaee F;Paglia DN;Yoshida R;Guzzo RM;Drissi H
通讯作者：
Drissi H
影响因子：
4.1
作者：
Kopher, Ross A.;Penchev, Vesselin R.;Islam, Mohammad S.;Hill, Katherine L.;Khosla, Sundeep;Kaufman, Dan S.
通讯作者：
Kaufman, Dan S.
影响因子：
4
作者：
Kimbrel, Erin A.;Kouris, Nicholas A.;Lanza, Robert
通讯作者：
Lanza, Robert
影响因子：
6
作者：
Chen, Yen Shun;Pelekanos, Rebecca A.;Fisk, Nicholas M.
通讯作者：
Fisk, Nicholas M.
DOI：
10.1159/000151746
发表时间：
2009
期刊：
Cells, tissues, organs
影响因子：
--
作者：
Brown SE;Tong W;Krebsbach PH
通讯作者：
Krebsbach PH