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.

中文翻译：

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HOXC10促进绵羊骨髓间充质干细胞的增殖并减少脂质积累。

含Homeodomain的基因C10（HOXC10）已知可调节细胞分化和增殖，是小鼠白色脂肪组织褐变的关键负调节剂。绵羊是一种重要的牲畜，提供人类食用的肉，脂肪含量是决定肉质的重要因素。但是，没有关于HOXC10在绵羊脂肪细胞或脂肪形成中的作用的报道。在这项研究中，我们调查了HOXC10对绵羊骨髓间充质干细胞（sBMSCs）增殖和成脂分化的影响。在sBMSCs中，HOXC10的过表达促进细胞增殖并上调p-PI3K，p-AKT，p-p70S6K，p-MEK和p-ERK的表达，而HOXC10敲低与相反的作用相关。这些结果表明HOXC10可能通过激活MEK / ERK和PI3K / AKT / mTOR / p70S6K信号通路来促进细胞增殖。此外，我们发现HOXC10表达与成脂分化的sBMSCs中的脂质蓄积负相关。sBMSC中HOXC10的过表达显着降低了脂质滴的积累并抑制了成脂特异性基因（包括ACC，LPL，PPARG和FABP4）的表达，而HOXC10的降低与相反的作用相关。此外，我们的研究提出了HOXC10对脂质蓄积和代谢影响的新调控机制。HOXC10可能至少部分地通过抑制LPL表达来负调节脂肪形成的sBMSC中的脂质蓄积。全面的，