Molecular profiling of adipose tissue-derived stromal cells cultured in hepatogenic medium

Adipose tissue-derived mesenchymal stromal cells (ATSC) hold great promises in regenerative medicine, due to their easy retrieval, their high proliferative capacity, and overall, their multi-lineages differentiation potential. In the last decade, several studies have reported the plasticity of ATSC toward a hepatic fate. Nonetheless, the molecular mechanisms allowing the conversion from a mesenchymal to an epithelial phenotype remain poorly understood. In this study, we investigated the full genome expression profiles of ATSC cultured for 4 weeks under pro-hepatogenic condition in comparison to control ATSC. Sets of differentially expressed genes were then functionally categorized to understand which pathways trigger the hepatic conversion. We showed that ATSC-derived hepatocyte-like cells overexpress sets of genes associated with hepatic functions, including protein metabolism, innate immune response regulation, and biodegradation of toxic compounds. Furthermore, microarray analysis highlighted the downregulation of several transcripts involved in stemness maintenance along with genes associated with the epithelial-mesenchymal-transition. Taken together, these data suggest that in vitro hepatogenic differentiation converts ATSC into immature hepatic cells, functionally related to liver progenitor cells. Adipose tissue was obtained from 2 patients (1 male, 1 female, mean age: 47 year old) undergoing partial abdominoplasty. Adipose tissue-derived stromal cells (ATSC) were isolated according to standard procedures, using the in vitro adherence property of these cells. At passage culture 4, ATSC were submitted to an in vitro hepatogenic regimen, consisting of the sequential addition of growth factors. After 1 month of in vitro differentiation, cells were harvested and their transcriptome was compared to control ATSC.