title: Development of a conditionally immortalized human pancreatic β cell line.
abstract: Diabetic patients exhibit a reduction in β cells, which secrete insulin to help regulate glucose homeostasis; however, little is known about the factors that regulate proliferation of these cells in human pancreas. Access to primary human β cells is limited and a challenge for both functional studies and drug discovery progress. We previously reported the generation of a human β cell line (EndoC-βH1) that was generated from human fetal pancreas by targeted oncogenesis followed by in vivo cell differentiation in mice. EndoC-βH1 cells display many functional properties of adult β cells, including expression of β cell markers and insulin secretion following glucose stimulation; however, unlike primary β cells, EndoC-βH1 cells continuously proliferate. Here, we devised a strategy to generate conditionally immortalized human β cell lines based on Cre-mediated excision of the immortalizing transgenes. The resulting cell line (EndoC-βH2) could be massively amplified in vitro. After expansion, transgenes were efficiently excised upon Cre expression, leading to an arrest of cell proliferation and pronounced enhancement of β cell-specific features such as insulin expression, content, and secretion. Our data indicate that excised EndoC-βH2 cells are highly representative of human β cells and should be a valuable tool for further analysis of human β cells.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Scharfmann
authors.forename: Severine
authors.initials: S
authors.lastname: Pechberty
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Hazhouz
authors.forename: Manon
authors.initials: M
authors.lastname: von Bülow
authors.forename: Emilie
authors.initials: E
authors.lastname: Bricout-Neveu
authors.forename: Maud
authors.initials: M
authors.lastname: Grenier-Godard
authors.forename: Fanny
authors.initials: F
authors.lastname: Guez
authors.forename: Latif
authors.initials: L
authors.lastname: Rachdi
authors.forename: Matthias
authors.initials: M
authors.lastname: Lohmann
authors.forename: Paul
authors.initials: P
authors.lastname: Czernichow
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravassard
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed / Q000166:cytology* / Q000378:metabolism; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000096:biosynthesis; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice
chemical_list: D007328:Insulin