IFATS Series: Stem Cell Antigen-1 Positive Ear Mesenchymal Stem Cells (EMSC) Display Enhanced Adipogenic Potential

Hyperplasia is a major contributor to the increase in adipose tissue mass that is characteristic of obesity. However, the identity and characteristics of cells that can be committed into adipocyte lineage remains unclear. Stem cell antigen 1 (Sca-1) has been used recently as a candidate marker in the search for tissue-resident stem cells. In our quest for biomarkers of cells that can become adipocytes, we analyzed ear mesenchymal stem cells (EMSC) that can differentiate into adipocytes, osteocytes, chondrocytes and myocytes. Our previous studies have demonstrated that EMSC abundantly expressed Sca-1. In the present study, we have analyzed the expression of adipogenic transcription factors and adipocyte-specific genes in Sca-1 enriched and Sca-1 depleted EMSC fractions. We found that Sca-1 enriched but not Sca-1 depleted EMSC showed a greater accumulation of lipid droplets during adipogenic differentiation. Similarly, EMSC isolated from Sca-1(-/-) mice displayed reduced lipid accumulation relative to EMSC from wild type controls (p < 0.01). Comparative analysis of the adipogenic differentiation process between Sca-1 enriched and Sca-1 depleted population of EMSC revealed substantial differences in the gene expression. Pref-1, C/EBPbeta, C/EBPalpha, PPARgamma2, LPL and aP2 were expressed at significantly higher levels in Sca-1 enriched EMSC fraction. However the most striking observation was that leptin was detected only in the conditioned media of Sca-1 enriched EMSC. Additionally, we performed loss-of-function (Sca-1 morpholino antisense oligonucleotides) experiments. The presented data suggest that Sca-1 is a biomarker for EMSC with the potential to become functionally active adipocytes.