title: Reprogrammed Stomach Tissue as a Renewable Source of Functional β Cells for Blood Glucose Regulation.
abstract: The gastrointestinal (GI) epithelium is a highly regenerative tissue with the potential to provide a renewable source of insulin(+) cells after undergoing cellular reprogramming. Here, we show that cells of the antral stomach have a previously unappreciated propensity for conversion into functional insulin-secreting cells. Native antral endocrine cells share a surprising degree of transcriptional similarity with pancreatic β cells, and expression of β cell reprogramming factors in vivo converts antral cells efficiently into insulin(+) cells with close molecular and functional similarity to β cells. Induced GI insulin(+) cells can suppress hyperglycemia in a diabetic mouse model for at least 6 months and regenerate rapidly after ablation. Reprogramming of antral stomach cells assembled into bioengineered mini-organs in vitro yielded transplantable units that also suppressed hyperglycemia in diabetic mice, highlighting the potential for development of engineered stomach tissues as a renewable source of functional β cells for glycemic control.
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
authors.forename: Chaiyaboot
authors.initials: C
authors.lastname: Ariyachet
authors.affiliation: Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Alessio
authors.initials: A
authors.lastname: Tovaglieri
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Guanjue
authors.initials: G
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Lu
authors.affiliation: Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Manasvi S
authors.initials: MS
authors.lastname: Shah
authors.affiliation: Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Division of Gastroenterology, Boston Children's Hospital, Boston, MA 02115, USA.
authors.forename: Camilla A
authors.initials: CA
authors.lastname: Richmond
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Catia
authors.initials: C
authors.lastname: Verbeke
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Melton
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ben Z
authors.initials: BZ
authors.lastname: Stanger
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: David
authors.initials: D
authors.lastname: Mooney
authors.affiliation: Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Ramesh A
authors.initials: RA
authors.lastname: Shivdasani
authors.affiliation: Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Shaun
authors.initials: S
authors.lastname: Mahony
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Breault
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: qiao_zhou@harvard.edu.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming; D000067470:Cellular Reprogramming Techniques; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D051379:Mice