Abstract
BackgroundMesenchymal 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.MethodsThe expression level of YAP during MSC differentiation was modulated using pharmaceutical molecule and genetic experiments through gain- and loss-of-function approaches.ResultsWe 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.ConclusionsThese 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.
Highlights
Mesenchymal stem cells (MSCs) are multipotent stem cells that are able to differentiate into several cell types, including cartilage, fat, and bone
To determine whether Yes-associated protein (YAP) was expressed in MSCs, we first determined the expression of YAP across cell types, including induced pluripotent stem cells (iPSCs), HEK293, and MSCs (Additional file 2: Figure S2)
The results showed YAP to be highly expressed in MSCs and that it could be used as a model for studying the effect of small molecules on MSC differentiation
Summary
Mesenchymal stem cells (MSCs) are multipotent stem cells that are able to differentiate into several cell types, including cartilage, fat, and bone. The non-canonical role of YAP in regulating bone homeostasis by promoting osteogenesis and suppressing adipogenesis was recently demonstrated in a mouse model. It is unclear whether YAP is crucial for modulating human MSC differentiation to fat and bone. YAP and transcriptional co-activator with PDZ-binding motif (TAZ), known as WW domain-containing transcriptional regulator 1 (WWTR1), were recently suggested as key regulators of bone homeostasis in mice by promoting osteogenesis and suppressing adipogenesis via the Smad or beta-catenin signaling pathway [17,18,19]. Whether or not YAP plays a role in controlling the adipo-osteogenic balance of human MSCs has never been reported
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