HOXC10 promotes proliferation and attenuates lipid accumulation of sheep bone marrow mesenchymal stem cells. (February 2020)

• Record Type: Journal Article
• Authors: Ma, Min; Wang, Cuiru; Ao, Yue; He, Nimantana; Hao, Fei; Liang, Hao; Liu, Dongjun
• Is Part Of: Molecular and cellular probes. Volume 49(2020)
• Publication Date: 2020-02
• Subjects: HOXC10 -- LPL -- Lipid accumulation -- Adipogenetic differentiation -- Proliferation -- Sheep BMSCs; Molecular probes -- Diagnostic use -- Periodicals; Pathology, Cellular -- Technique -- Periodicals; Cell Biology -- Periodicals; Molecular Biology -- Periodicals; Sondes moléculaires -- Utilisation diagnostique -- Périodiques; Cytopathologie -- Technique -- Périodiques; 572
• DOI: 10.1016/j.mcp.2019.101491
• Languages: English
• ISSNs: 0890-8508

Abstract

Abstract: Homeodomain-containing gene C10 ( HOXC10 ), known to regulate cell differentiation and proliferation, is a key negative regulator in the browning of white adipose tissue in mice. Sheep is an important farm animal that provides meat for human consumption, with fat content being an important meat quality determinant; however, there is no report about the role of HOXC10 in sheep adipocytes or adipogenesis. In this study, we investigated the effect of HOXC10 on proliferation and adipogenic differentiation in sheep bone marrow mesenchymal stem cells (sBMSCs). In sBMSCs, HOXC10 overexpression promoted cell proliferation and upregulated the expression of p-PI3K, p-AKT, p-p70S6K, p-MEK, and p-ERK, whereas HOXC10 knockdown was associated with the opposite effects. These results suggested that HOXC10 may promote cell proliferation by activating the MEK/ERK and PI3K/AKT/mTOR/p70S6K signaling pathways. In addition, we found that HOXC10 expression was negatively associated with lipid accumulation in adipogenic-differentiated sBMSCs. HOXC10 overexpression in sBMSCs significantly decreased lipid droplet accumulation and suppressed the expression of adipogenic-specific genes, including ACC, LPL, PPARG, and FABP4, while HOXC10 knockdown was associated with the opposite effects. Furthermore, our study suggested a new regulatory mechanism of the effect of HOXC10 on lipid accumulation and metabolism; HOXC10 may negatively regulate lipid accumulation in adipogenic-differentiated sBMSCs, at least in part, by suppressing LPL expression. Overall, our research not only contributes to a better understanding of the mechanism of lipid accumulation and metabolism in sheep, but also shed light on meat quality control in the future. Highlights: HOXC10 promotes cell proliferation of sheep BMSCs. HOXC10 may induce cell proliferation via MAPK and AKT signaling pathways. HOXC10 reduces lipid drop formation and suppresses adipogenic-specific genes in sheep BMSCs. HOXC10 impairs lipid accumulation in adipogenic-differentiated sheep BMSCs by targeting LPL .