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Journal of Diabetes Research
Volume 2017, Article ID 6726901, 6 pages
Research Article

Forkhead Protein FoxO1 Acts as a Repressor to Inhibit Cell Differentiation in Human Fetal Pancreatic Progenitor Cells

1Shenzhen University Diabetes Institute, Shenzhen University, Shenzhen 518060, China
2Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China
3Shenzhen Hightide Biopharmaceutical Ltd., Shenzhen 518000, China
4Department of Aging Medicine, The Sixth Hospital of Shenzhen Municipality, Shenzhen 518060, China

Correspondence should be addressed to Xiaosong Ma; nc.ude.uzs@amsx

Received 13 October 2016; Revised 27 December 2016; Accepted 29 January 2017; Published 28 February 2017

Academic Editor: Andrea Tura

Copyright © 2017 Zongzhe Jiang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 pancreatic cell 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 mature β cells. On the contrary, overexpression of FoxO1 suppressed the induction and reduced expression of these β cell markers. Taken together, these results suggest that FoxO1 may act as a repressor to inhibit cell differentiation in human fetal pancreatic progenitor cells.