Efficient generation of pancreatic β-like cells from the mouse gallbladder.
Direct reprogramming is a promising approach for the replacement of β cells in diabetes. Reprogramming of cells originating from the endodermal lineage, such as acinar cells in the pancreas, liver cells and gallbladder cells has been of particular interest because of their developmental proximity to β cells. Our previous work showed that mouse gallbladder epithelium can be partially reprogrammed in vitro to generate islet-like cells (rGBC1). Here, the reprogramming protocol was substantially improved, yielding cells (rGBC2) closer to functional β cells than the 1st generation method with higher conversion efficiency and insulin expression. In addition to insulin synthesis and processing, rGBC2 presented many hallmark features of β cells, including insulin secretion in response to high glucose stimulation. Gene expression analysis indicated that rGBC2 clustered closer with β cells and had a metabolic gene expression profile resembling neonatal β cells. When transplanted into immune-deficient animals, rGBC2 were stable for at least 5months and further matured in vivo. Taken together, this approach provides further understanding of endodermal lineage conversion and potential for development of cell replacement therapy for type 1 diabetes patients.
Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland, OR, USA. Electronic address: wangyuh@ohsu.edu.
Yuhan
Y
Wang
Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland, OR, USA.
Feorillo
F
Galivo
Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland, OR, USA.
Carl
C
Pelz
Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland, OR, USA.
Annelise
A
Haft
Department of Developmental Biology, Department of Medicine (Division of Oncology), Stanford University School of Medicine, Stanford, CA, USA.
Jonghyeob
J
Lee
Department of Developmental Biology, Department of Medicine (Division of Oncology), Stanford University School of Medicine, Stanford, CA, USA.
Seung K
SK
Kim
Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland, OR, USA. Electronic address: grompem@ohsu.edu.
Markus
M
Grompe
D000818:Animals; D065150:Cellular Reprogramming / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D005704:Gallbladder / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD
D007328:Insulin
Gallbladder; Insulin; Pancreatic beta cells; Reprogramming; Type 1 diabetes