Regulation of differentiation of mesenchymal stem cells by the Hippo pathway effectors TAZ/YAP

Abstract

Mesenchymal stem cells (MSCs) are pluripotent cells which can differentiate into several distinct lineages, such as chondrocytes, adipocytes and myofibers. It has been reported that the lineage-specific transcriptional factors including Runt related transcription factor 2 (RUNX2), Peroxisome proliferator-activator receptor gamma (PPARgamma) and Myogenic differentiation 1 (MyoD) may play key regulatory roles among the differentiation of MSCs. Recently, researches have confirmed that the Hippo pathway impacts the differentiation fates of MSCs through regulating the activity of line- age-specific transcription factors by the Hippo pathway effectors Tafazzin (TAZ) and/or Yes-associated protein (YAP). The interaction between TAZ and RUNX2 boosts the osteogenic processes and promotes MSCs differentiating into osteoblast lineage. However, PPARgamma binding to TAZ may inhibit the adipocytes differentiation, and thus overexpression of TAZ in mesenchymal stem cell-like cells increases the expression of myogenic genes and hastens myofiber formation through a MyoD-dependent manner. Moreover, other signaling pathways (such as BMP-2, TNF-alpha, Eph-Ephrin, etc.), small molecules (KR62980, TM-25659, etc.), and mechanistic stimuli can also affect the fate by regulating the activity of TAZ/YAP. In this review, we summarized the signaling pattern of Hippo pathway and the function mechanism of TAZ and/or YAP by enumerating their interaction to several lineage-specific transcriptional factors and relationship with other signal pathways during MSCs differentiation.

Type I collagen inhibits adipogenic differentiation via YAP activation in vitro

“…It was reported that ****LATS (inhibitory kinase of YAP) could modulate adipocyte proliferation and differentiation via hippo signaling. Although YAP regulates differentiation in many cells such as mesenchymal stem cells (Men, Piao, & Teng, 2013), epithelial progenitors (Mahoney, Mori, Szymaniak, Varelas, & Cardoso, 2014) and retinal progenitors (Asaoka, Hata, Namae, Furutani-Seiki, & Nishina, 2014), the effect of YAP on adipogenic differentiation of preadipocyte is poorly understood.…”

Bushen-Qiangdu-Zhilv decoction inhibits osteogenic differentiation of rat fibroblasts by regulating connexin 43

“…2). The mean of inhibition rate for each group was 0.07% (25 µg/ml), 4.13% (50 µg/ml), 6.79% (100 µg/ml), 12.38% (200 µg/ml), 18.79% (500 µg/ml) and 13.63% (750 µg/ml). BQZ at concentrations of 100, 200, 500 and 750 µg/ml could significantly inhibit the proliferation of fibroblast cells (P<0.05).…”

YAP increases response to Trastuzumab in HER2-positive Breast Cancer by enhancing P73-induced apoptosis

“…Yes-associated protein (YAP), a downstream effector molecule of the Hippo signaling pathway, serves as a transcriptional coactivator and is reportedly expressed in many human malignancies [11][12][13], including breast cancer [14]. Nuclear-YAP (N-YAP) interacts with transcription factors and promotes cancer cell proliferation, while maintaining stemness and metastasis [15][16][17][18][19]. Furthermore, its nuclear abundance was reported to correlate with tumor progression and decreased survival in patients with breast cancer [20][21][22].…”