title: Functional signature of human islet-derived precursor cells compared to bone marrow-derived mesenchymal stem cells.
abstract: Pancreatic islet beta-cell replenishment can be driven by epithelial cells from exocrine pancreas via epithelial-mesenchymal transition (EMT) and the reverse process MET, while specified pancreatic mesenchymal cells control islet cell development and maintenance. The role of human islet-derived precursor cells (hIPCs) in regeneration and support of endocrine islets is under investigation. Here, we analyzed hIPCs as to their immunophenotype, multilineage differentiation capacity, and gene profiling, in comparison to human bone marrow-derived mesenchymal stem cells (hBM-MSCs). hIPCs and hBM-MSCs display a common mesenchymal character and express lineage-specific marker genes upon induction toward pancreatic endocrine and mesenchymal pathways of differentiation. hIPCs can go further along endocrine pathways while lacking some core mesenchymal differentiation attributes. Significance analysis of microarray (SAM) from 5 hBM-MSC and 3 hIPC donors mirrored such differences. Candidate gene cluster analysis disclosed differential expression of key lineage regulators, indicated a HoxA gene-associated positional memory in hIPCs and hBM-MSCs, and showed as well a clear transition state from mesenchyme to epithelium or vice versa in hIPCs. Our findings raise new research platforms to further clarify the potential of hIPCs to undergo complete MET thus contributing to islet cell replenishment, maintenance, and function.
authors.affiliation: Orthopedic Center for Musculoskeletal Research, Stem Cell Division, Orthopedic Department, University of Würzburg, Würzburg, Germany.
authors.forename: Catarina
authors.initials: C
authors.lastname: Limbert
authors.forename: Regina
authors.initials: R
authors.lastname: Ebert
authors.forename: Tatjana
authors.initials: T
authors.lastname: Schilling
authors.forename: Gunter
authors.initials: G
authors.lastname: Path
authors.forename: Peggy
authors.initials: P
authors.lastname: Benisch
authors.forename: Ludger
authors.initials: L
authors.lastname: Klein-Hitpass
authors.forename: Jochen
authors.initials: J
authors.lastname: Seufert
authors.forename: Franz
authors.initials: F
authors.lastname: Jakob
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology*; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D046790:Pancreas, Exocrine / Q000166:cytology; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology