title: Forkhead Protein FoxO1 Acts as a Repressor to Inhibit Cell Differentiation in Human Fetal Pancreatic Progenitor Cells.
abstract: Our colleagues have reported previously that human pancreatic progenitor cells can readily differentiate into insulin-containing cells. Particularly, transplantation of these cell clusters upon in vitro induction for 3-4 w partially restores hyperglycemia in diabetic nude mice. In this study, we used human fetal pancreatic progenitor cells to identify the forkhead protein FoxO1 as the key regulator for cell differentiation. Thus, induction of human fetal pancreatic progenitor cells for 1 week led to increase of the pancreaticβcell markers such as Ngn3, but decrease of stem cell markers including Oct4, Nanog, and CK19. Of note, FoxO1 knockdown or FoxO1 inhibitor significantly upregulated Ngn3 and insulin as well as the markers such as Glut2, Kir6.2, SUR1, and VDCC, which are designated for matureβcells. On the contrary, overexpression of FoxO1 suppressed the induction and reduced expression of theseβcell markers. Taken together, these results suggest that FoxO1 may act as a repressor to inhibit cell differentiation in human fetal pancreatic progenitor cells.
authors.affiliation: Shenzhen University Diabetes Institute, Shenzhen University, Shenzhen 518060, China.
authors.forename: Zongzhe
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Shenzhen University Diabetes Institute, Shenzhen University, Shenzhen 518060, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Tian
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Shenzhen University Diabetes Institute, Shenzhen University, Shenzhen 518060, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yan
authors.affiliation: Shenzhen Hightide Biopharmaceutical Ltd., Shenzhen 518000, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Aging Medicine, The Sixth Hospital of Shenzhen Municipality, Shenzhen 518060, China.
authors.forename: Zhenhe
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Jinning
authors.initials: J
authors.lastname: Lou
authors.affiliation: Shenzhen University Diabetes Institute, Shenzhen University, Shenzhen 518060, China.
authors.forename: Xiaosong
authors.identifier: 0000-0002-9527-0171
authors.initials: X
authors.lastname: Ma
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells; D064233:Sulfonylurea Receptors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000099161:Kcnj11 Channel
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015220:Calcium Channels; D000071161:Forkhead Box Protein O1; D051273:Glucose Transporter Type 2; D007328:Insulin; D009419:Nerve Tissue Proteins; D024661:Potassium Channels, Inwardly Rectifying; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human; C498695:NEUROG3 protein, human