UBC Theses and Dissertations
Identification, isolation and characterization of murine adult adipogenic progenitor cells Joe, Aaron Wai Bun
White adipose tissue, or fat, is a complex endocrine tissue important for energy storage and metabolism, and has significant effects on various physiological phenomena, including growth, behaviour, reproduction and immune-modulation. It has been proposed that fat cells, or adipocytes, arise from connective tissue cells that fill with lipid; however, mounting evidence suggests that adipocytes represent a distinct lineage with its own cellular origins. Yet very little is known about the cells that give rise to new adipocytes. Here, my colleagues and I developed a strategy to isolate purified populations of adipogenic progenitor (AP) cells from subcutaneous fat, visceral fat and skeletal muscle, using fluorescence-activated cell sorting. These cells are capable of robust adipogenic differentiation, even at the single cell level. We confirmed their commitment to the adipogenic lineage using a variety of assays, and reveal that they are lineage-restricted cells, incapable of osteogenic, chondrogenic or myogenic differentiation. Thus, we have developed an enabling technology to allow interrogation of the adipocyte lineage among different tissues and fat depots, during different physiological, pathological or developmental stages. Recent evidence suggests that fat depots with a greater ability to generate new adipocytes are associated with lower metabolic risk. Using our isolation strategy, we confirmed that metabolically healthier depots are associated with greater AP abundance and activity, uncovering a link between stem cell biology and metabolic disease. However, adipocyte production in non-adipose tissues, such as skeletal muscle and bone marrow, is associated with chronic disease and aging. To explore possible reasons for this dichotomy, we examined the role of APs in a model of skeletal muscle injury. Our results suggest that APs expand after damage to assist in muscle regeneration by establishing a pro-myogenic niche, ascribing to them a novel function that is independent of adipogenesis. Together, our strategy to interrogate the adipogenic lineage has allowed us to formulate new hypotheses to explain adipose and skeletal muscle physiology. This technology forms the basis for future work that will to allow us to understand how new adipocytes are formed, and perhaps permit the manipulation of adipogenic progenitors for therapeutic benefit.
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