53 Distinct adipogenic and fibrogenic differentiation potentials in mesenchymal stromal cells from pancreas and white adipose tissue

Background

Apart from white adipose tissue (WAT), adipose accretion also occurs in non-adipose tissue, such as the pancreas. To date, the role of pancreatic fat cells in T2D development remains elusive. Recently, we reported that genetically diabetes-prone mice exhibit more pancreatic adipocytes than diabetes-resistant mice. Further we showed that co-culture of pancreatic islets and adipocytes derived from mesenchymal stromal cells (MSCs) of the pancreas and inguinal WAT (iWAT) results in hypersecretion of insulin. However, the role of pancreas MSCs in modulating organ health is still unclear. The aim of this study was to elucidate the transcriptional and regulatory differences, and downstream effects on differentiation capacities and organ function, between pancreas and iWAT MSCs.

Methods

Diabetes-resistant B6 mice were used to sort defined populations of pancreatic and iWAT MSCs by fluorescence-activated cell sorting and to perform miRNome and transcriptome analysis. Bioinformatic tools like gene ontology (GO) and ingenuity pathway analyses were conducted to gain further insight into biological processes and pathways potentially involved in distinct cell-type processes. Pancreas and iWAT MSCs from B6 and diabetes-prone NZO mice were further characterized by in-vitro and ex-vivo assays to determine tissue-specific cell fates and islet function.

Results

Transcriptome and miRNome analyses displayed 1227 differentially expressed genes (DEGs) and 121 differentially expressed miRNAs between pancreas and iWAT MSCs. Target prediction analysis estimated that more than 40% (510 genes) of the DEGs could be regulated by 58 differentially expressed miRNAs. Furthermore, various miRNAs were exclusively expressed in pancreas or iWAT MSCs. GO-analyses of DEGs and miRNA target genes showed unique transcriptional and miRNA signatures in pancreas and iWAT MSCs, including fibrogenic and adipogenic differentiation, respectively. Functional analyses of adipogenic and fibrogenic differentiation capacities in diabetes-prone and diabetes-resistant mice depicted a markedly lower adipogenic lineage commitment with a simultaneously increased fibrogenic differentiation in pancreas MSCs but no strain-specific differences.

Conclusion

Pancreas and iWAT MSCs exhibit highly differential transcriptome and miRNome profiles presumably determining distinctive cell lineage fates. Independent of diabetes-susceptibility, pancreas MSCs displayed low adipogenic and increased fibrogenic differentiation capacity, while iWAT MCS showed preference for adipogenic lineage commitment. Thus, elevated pancreas adipogenesis in diabetes-prone animals has to be mediated by other factors.

Publication History

Article published online:
24 September 2021