Regulation of chicken mesenchymal stem cells by bioactive molecules

间充质干细胞（MSC）是存在于血液、骨、脂肪组织、肌肉和软骨中的多能祖细胞。MSC是成骨细胞和脂肪细胞的共同祖细胞，并且已经证明MSC的成骨分化和成脂分化之间的相互关系。MSC向特定细胞类型的谱系特异性分化的控制通过基因表达的特异性主调节剂实现，例如用于脂肪细胞分化的过氧化物酶体增殖物激活受体γ（PPAR-gamma）和用于成骨细胞分化的Runx 2。更好地了解生物活性分子，调节这种主调节分化是至关重要的，以提高我们目前的MSC调节知识，改善动物生长和骨骼健康。特异性氧化固醇是调节MSC分化的潜在生物活性分子。氧固醇是胆固醇的27个碳氧化产物的大家族，存在于人和动物的循环和组织中。我已经报道了特定的氧固醇通过抑制脂肪生成的主要调节因子PPAR-gamma的表达来抑制小鼠MSC的脂肪生成分化，同时诱导这些细胞中的成骨分化。最近，我发现特定氧固醇的促成骨和抗脂肪形成作用是通过小鼠MSC中的Hh和/或Notch信号传导激活介导的。由于Hh和Notch信号通路在动物物种中是保守的，因此重要的是理解特定氧固醇通过Hh和Notch通路激活对鸡MSC的调节。该研究的长期目标是了解生物活性分子对鸡间充质干细胞的调节，并确定间充质干细胞对动物生长和健康的影响。我相信，我的研究将提供更好地了解生物活性分子调控MSC的成骨和成脂分化的分子机制，并对扩大MSC调控的基础知识具有重要意义。

Mesenchymal stem cells (MSC) are multipotent progenitor cells that are present in blood, bone, adipose tissue, muscle, and cartilage. MSC are common progenitors of osteoblasts and adipocytes, and a reciprocal relationship between osteogenic and adipogenic differentiation of MSC has been demonstrated. The control of lineage specific differentiation of MSC into specific cell types is achieved through specific master regulators of gene expression such as peroxisome proliferator-activated receptor gamma (PPAR-gamma) for adipocyte differentiation and Runx2 for osteoblast differentiation. Better understanding of bioactive molecules that regulate such master regulators of differentiation is vital to enhance our current knowledge of MSC regulation and improve animal growth and skeletal health. Specific oxysterols are potential bioactive molecules that can regulate MSC differentiation. Oxysterols, a large family of 27-carbon oxygenated products of cholesterol, are present in the circulation and tissues of human and animal. I have reported that specific oxysterols inhibit the adipogenic differentiation of mouse MSC by inhibiting the expression of PPAR-gamma, the master regulator of adipogenesis, while inducing osteogenic differentiation in these cells. Recently, I found that pro-osteogenic and anti-adipogenic effects of specific oxysterols are mediated through Hh and/or Notch signalling activation in mouse MSC. Since Hh and Notch signaling pathways are conservative among animal species, it is important to understand the regulation of chicken MSC by Hh and Notch pathway activation by specific oxysterols. The long-term goal of the proposed research is to understand the regulation of chicken mesenchymal stem cells by bioactive molecules and to determine the impact of mesenchymal stem cells on animal growth and health. I believe that my research will provide better understanding of the molecular mechanisms by which bioactive molecules regulate osteogenic and adipogenic differentiation of MSC and have significant implications for expanding the basic knowledge of MSC regulation for general biological sciences.