Epithelial-to-mesenchymal transition generates proliferative human islet precursor cells.
Insulin-expressing beta cells, found in pancreatic islets, are capable of generating more beta cells even in the adult. We show that fibroblast-like cells derived from adult human islets donated postmortem proliferate readily in vitro. These mesenchymal-type cells, which exhibit no hormone expression, can then be induced to differentiate into hormone-expressing islet-like cell aggregates, which reestablishes the epithelial character typical of islet cells. Immunohistochemistry, in situ hybridization, and messenger RNA measurements in single cells and cell populations establish the transition of epithelial cells within islets to mesenchymal cells in culture and then to insulin-expressing epithelial cells.
Gershengorn
Marvin C
MC
Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-8029, USA. marving@intra.niddk.nih.gov
Hardikar
Anandwardhan A
AA
Wei
Chiju
C
Geras-Raaka
Elizabeth
E
Marcus-Samuels
Bernice
B
Raaka
Bruce M
BM
D000293:Adolescent; D000328:Adult; D002096:C-Peptide / Q000096:biosynthesis / Q000235:genetics; D002449:Cell Aggregation; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016895:Culture Media, Serum-Free; D004847:Epithelial Cells / Q000166:cytology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D007633:Keratins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology*; D008875:Middle Aged; D011384:Proinsulin / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics
D002096:C-Peptide; D016895:Culture Media, Serum-Free; D007328:Insulin; D012333:RNA, Messenger; D014746:Vimentin; D007633:Keratins; D011384:Proinsulin