人多能干细胞具有体外自我复制以及分化为各种功能性终末分化细胞的潜能，分化产生的功能细胞对于研究人类发育、药物筛选以及疾病模拟等发挥了重要作用。但是，人多能干细胞如何分化为各种组织干细胞例如间充质干细胞一直以来研究很少。我们前期的研究结果表明转录因子MSX2在调控人多能干细胞早期三个胚层命运决定中发挥重要作用。同时，在人多能干细胞中持续过表达MSX2，可以诱导其分化为间充质干细胞样细胞。因此，本研究中我们计划首先利用MSX2作为编程因子，建立诱导人多能干细胞高效分化为间充质干细胞的体系。其次，通过CRISPR/CAS9、RNA-SEQ技术研究MSX2作为编程因子诱导人多能干细胞分化为间充质干细胞的分子机理。最后，我们将研究分化产生的间充质干细胞在人多能干细胞造血分化过程中的应用。我们的研究结果将为阐明人多能干细胞分化为间充质干细胞的机理以及其应用提供有益的启示。

Human pluripotent stem cells (hPSCs) hold the capacity to self-renew and differentiate into multiple lineages of functional cell types, which play essential roles in human development studying, drug screening and disease modeling. However, there has been limited progress in inducing hPSCs into adult stem cells, such as mesenchymal stem/stromal cells (MSCs). Our team previously reported that the transcription factor MSX2 played vital role in cell-fate determination of hPSCs into three germ layers. Recently, we further found continuous over-expression of MSX2 program hPSCs differentiating into MSC-like cells. Therefore, in this study, we will try to establish a novel differentiation system to generate MSCs efficiently from hPSCs by utilizing MSX2 as a programming factor. In addition, we aim to study the molecular mechanism in this process by taking advantage of the technology of CRISPR/Cas9 and RNA-SEQ. We will also test the hematopoiesis supporting potential of hPSCs-derived MSCs. Our results will reveal the molecular mechanism of inducing hPSCs into MSCs and shed light on its potential application in regenerative medicine.