Adipose tissue is a central component of whole-body energy homeostasis regulation. Advancement in understanding adipose tissue biology may provide new strategies for the intervention of obesity and obesity-related diseases. Adipogenesis is defined as a process through which new adipocytes are formed by differentiation of adipose-derived stem cells. Over the past two decades or so, many adipogenic regulators have been uncovered, however, few studies have focused on studying how different subcellular structures reorganize themselves during adipogenesis, which is accompanied by significant morphological changes. In addition, there is a lack of systematic understanding of the sequence of events underlying human adipogenesis that correlates molecular players with subcellular remodeling. In order to depict a blueprint of the cellular events underlying adipogenesis in a timely manner and incorporate the role of identified molecular players into these events, this study proposes to use adipogenic differentiation of human mesenchymal stem cells (hMSCs) as an in vitro model to examine the expression and function of a group of 14 actin-associated genes during adipogenesis as specific aim 1. This group of gene have been implicated in cytoskeleton organization and were identified through a unique combined approach of siRNA high throughput screen and microarray expression profiling, which provided high degree of confidence in the adipogenic relevance of the uncovered genes, as demonstrated by preliminary results on a group of cell cycle regulators identified through the same approach.
In specific aim 2, fluorescently labeled molecular probes will be used to live image the re- organization of related cellular structures plasma membrane and cytoskeleton, during normal as well as perturbed adipogenesis induced by functional manipulation of known or newly identified adipogenic regulators from aim 1. Knowledge gained from the proposed study will contribute to our fundamental understanding of human adipogenesis and stem cell biology and may provide new strategies for the intervention of obesity and obesity-related diseases. In addition, advancement in understanding adipose tissue biology may facilitate the process of in vitro adipose tissue engineering including breast tissue reconstruction for cancer patients and provide new biomarkers for studying the safety and toxicity of various pharmaceutical drugs, environmental chemicals or nutraceutical supplements on adipose tissue development.
This project is aimed to provide better understanding of the process of how human fat cells are formed. Knowledge gained from this proposed study may provide insights and useful tools for controlling fat tissue associated diseases such as obesity and diabetes, enhancing cell-based therapies such as breast tissue reconstruction for cancer patients, and predicting potential adverse effect of various pharmaceutical drugs, nutraceutical supplements and environmental chemicals on fat tissue development.