YAP1 promotes adipogenesis by regulating negative feedback mechanism of the hippo pathway via LATS2. YAP1 promotes adipogenesis by regulating negative feedback mechanism of the hippo pathway via LATS2

Adipose-derived mesenchymal stem cells (ADSCs) originating from adipose tissue are an important source of mesenchymal stem cells (MSCs) with multidirectional differentiation potential. YAP, a key effector of the Hippo signaling pathway, can control and regulate the differentiation of MSCs to certain types of mature cells. However, the specific mechanism of ADSCs' lipidogenic differentiation has not been clearly concluded. In this study, we used Capra hircus ADSCs (gADSCs) from Albas in Inner Mongolia as experimental materials. YAP1 promoted the differentiation of ADSCs into adipocytes. YAP1 overexpression activated the negative feedback regulation of the Hippo signaling pathway. LATS2 phosphorylation levels in the cells increased after YAP1 overexpression, leading to YAP phosphorylation, which reduces YAP and TAZ levels in the nucleus while promoting their accumulation in the cytoplasm. YAP1 overexpression increased the expression of LATS2, and overexpression of LATS2 promoted the differentiation of ADSCs to adipocytes. The promotion of ADSCs adipose differentiation by YAP1 was affected by the activity of LATS2 kinase. Therefore, overexpression of YAP1 promotes ADSCs adipogenic differentiation by regulating the expression of LATS2 and activating the negative feedback of Hippo pathway. Elucidating the molecular mechanism of YAP in ADSCs lipogenic differentiation is of great significance for the regulation of stem cell differentiation homeostasis, disease treatment and hair follicle growth. Overall design: To investigate the effect of YAP on adipogenesis of gADSCs, we constructed gADSCs cell lines OE-TAZ. RNA-seq was performed with OE-TAZ and Control cells. Based on the RNA-seq data, an expression profile was generated.