Regulation of chicken mesenchymal stem cells by bioactive molecules

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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.