Siriraj Center of Excellence for Stem Cell Research, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand.
Synchrotron Light Research Institute (Public Organization), Nakhon Ratchasima, Thailand.
Stem Cell Res Ther. 2019 Dec 18;10(1):402. doi: 10.1186/s13287-019-1494-4.
Mesenchymal stem cells (MSCs) are multipotent stem cells that are able to differentiate into several cell types, including cartilage, fat, and bone. As a common progenitor, MSC differentiation has to be tightly regulated to maintain the balance of their differentiation commitment. It has been reported that the decision process of MSCs into fat and bone cells is competing and reciprocal. Several factors have been suggested as critical factors that affect adipo-osteogenic decision, including melatonin and smad4. Yes-associated protein (YAP) is an important effector protein in the Hippo signaling pathway that acts as a transcriptional regulator by activating the transcription of the genes involved in cell proliferation and anti-apoptosis. The non-canonical role of YAP in regulating bone homeostasis by promoting osteogenesis and suppressing adipogenesis was recently demonstrated in a mouse model. However, it is unclear whether YAP is also crucial for modulating human MSC differentiation to fat and bone.
The expression level of YAP during MSC differentiation was modulated using pharmaceutical molecule and genetic experiments through gain- and loss-of-function approaches.
We demonstrated for the first time that YAP has a non-canonical role in regulating the balance of adipo-osteogenic differentiation of human MSCs. The result from synchrotron radiation-based Fourier transform infrared (FTIR) microspectroscopy showed unique metabolic fingerprints generated from YAP-targeted differentiated cells that were clearly distinguished from non-manipulated control.
These results, thus, identify YAP as an important effector protein that regulates human MSC differentiation to fat and bone and suggests the use of FTIR microspectroscopy as a promising technique in stem cell research.
间充质干细胞（MSCs）是多能干细胞，能够分化为多种细胞类型，包括软骨、脂肪和骨骼。作为一个共同的祖细胞，MSC 的分化必须受到严格的调控，以维持其分化的平衡。据报道，MSC 向脂肪细胞和骨细胞的分化过程是竞争和相互制约的。已经有研究报道了一些关键因素，如褪黑素和 Smad4，它们影响脂肪和成骨细胞的定向分化。Yes 相关蛋白（YAP）是 Hippo 信号通路中的一个重要效应蛋白，通过激活参与细胞增殖和抗凋亡的基因的转录，充当转录调节因子。最近在小鼠模型中证明了 YAP 在通过促进成骨和抑制成脂来调节骨稳态方面的非经典作用。然而，目前尚不清楚 YAP 是否对调节人 MSC 向脂肪和骨骼的分化也很重要。
通过药物分子和遗传实验，通过增益和失能方法来调节 MSC 分化过程中 YAP 的表达水平。
我们首次证明 YAP 在调节人 MSC 脂肪和成骨分化的平衡中具有非经典作用。基于同步辐射的傅里叶变换红外（FTIR）微光谱的结果显示，源自 YAP 靶向分化细胞的独特代谢指纹图谱与未受干预的对照细胞明显区分开来。
这些结果表明，YAP 是一种调节人 MSC 向脂肪和骨骼分化的重要效应蛋白，并表明 FTIR 微光谱学作为一种有前途的干细胞研究技术的应用。
