Depot-dependent regulation of adipose stem cell functions by CD10

Abstract

Obesity related cardiovascular and metabolic diseases are associated with visceral (VS) rather than subcutaneous (SC) obesity. Unlike VS fat, SC fat displays better adipogenic potential and lesser lipolytic activities, thus is able to accommodate excess lipids, and prevents ectopic lipids deposition to other organs and subsequent metabolic complications. Recently, SC-adipose-derived stem cell (ASC) was discovered to express higher level of CD10 than VS-ASC. Also, a positive correlation between CD10 expression level and lipid accumulation during adipogenesis is established. Therefore, to determine the functional relevance of CD10 in ASCs, we created CD10-knockdown (CD10-KD) and CD10-overexpression (CD10-OE) ASCs, and subjected them to trilineage differentiation into adipocytes, osteocytes and chondrocytes. CD10-KD-ASC had significant reduction in lipid accumulation during adipogenesis and the contrary was observed in CD10-OE-SC-ASC as indicated by the preliminary data. Interestingly, this lipid accumulation defect was independent of the major adipogenic genes, such as ZFP423, PPARγ and aP2, and hypothesized to involve dysregulation of lipolysis due to CD10-KD. Next, we demonstrated the importance of CD10 in osteogenesis, as CD10-KD in ASCs impeded its differentiation potential into osteocytes. Lastly, our preliminary result suggested that CD10 was not essential for chondrocytes formation, as CD10-KD-ASC was able to differentiate into chondrocytes.