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Islet cell differentiation in liver by combinatorial expression of transcription factors Neurogenin-3, BETA2, and RIPE3b1

Authors
 Young-Duk Song  ;  Eun-Jig Lee  ;  J. Larry Jameson  ;  So-Youn Kim  ;  Liza E. Pfaff  ;  Parham Yashar 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.354(2) : 334-339, 2007 
Journal Title
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 
ISSN
 0006-291X 
Issue Date
2007
Abstract
Transcription factors, such as PDX-1, that normally mediate pancreatic development are capable of inducing hepatic progenitor cells to differentiate into cells with pancreatic islet characteristics. We hypothesized that simultaneous expression of multiple transcription factors involved in islet development might enhance the differentiation of hepatic progenitor cells. Bi- or tri-cistronic constructs were generated in hybrid adenovirus/adeno-associated virus (Ad/AAV) vectors containing neurogenin 3 (NGN3), BETA2 (NeuroD), and RIPE3b1 (MafA), each of which plays a role in islet cell differentiation. These vectors efficiently express multiple transcription factors and stimulate insulin promoter activity in a combinatorial manner. When these multi-cistronic constructs were administered in vivo, they induce hepatic expression of islet-specific markers, including PDX-1, insulin, glucagon, somatostatin, and islet-amyloid peptide. Administration of the Ad/AAV hybrid vectors to streptozotocin-induced diabetic mice reversed hyperglycemia, consistent the differentiation of functional hepatic insulin-secreting cells. These results indicate that Ad/AAV hybrid vectors can be used to administer combinations of factors that induce islet cell differentiation in hepatic progenitor cells.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X06027975
DOI
10.1016/j.bbrc.2006.12.216
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Eun Jig(이은직) ORCID logo https://orcid.org/0000-0002-9876-8370
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/95687
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