Document Detail


In vivo reprogramming of adult pancreatic exocrine cells to beta-cells.
MedLine Citation:
PMID:  18754011     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
One goal of regenerative medicine is to instructively convert adult cells into other cell types for tissue repair and regeneration. Although isolated examples of adult cell reprogramming are known, there is no general understanding of how to turn one cell type into another in a controlled manner. Here, using a strategy of re-expressing key developmental regulators in vivo, we identify a specific combination of three transcription factors (Ngn3 (also known as Neurog3) Pdx1 and Mafa) that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble beta-cells. The induced beta-cells are indistinguishable from endogenous islet beta-cells in size, shape and ultrastructure. They express genes essential for beta-cell function and can ameliorate hyperglycaemia by remodelling local vasculature and secreting insulin. This study provides an example of cellular reprogramming using defined factors in an adult organ and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.
Authors:
Qiao Zhou; Juliana Brown; Andrew Kanarek; Jayaraj Rajagopal; Douglas A Melton
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-08-27
Journal Detail:
Title:  Nature     Volume:  455     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-03     Completed Date:  2008-11-13     Revised Date:  2011-06-01    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  627-32     Citation Subset:  IM    
Affiliation:
Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE12025
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MeSH Terms
Descriptor/Qualifier:
Aging / physiology
Animals
Basic Helix-Loop-Helix Transcription Factors / genetics,  metabolism
Biological Markers / analysis
Cell Shape
Cell Size
Cell Transdifferentiation*
Homeodomain Proteins / genetics,  metabolism
Hyperglycemia / metabolism
Insulin / metabolism
Insulin-Secreting Cells / cytology*,  metabolism,  ultrastructure
Maf Transcription Factors, Large / genetics,  metabolism
Mice
Neovascularization, Physiologic
Nerve Tissue Proteins / genetics,  metabolism
Pancreas, Exocrine / cytology*,  embryology,  secretion
Regenerative Medicine / methods
Trans-Activators / genetics,  metabolism
Transcription Factors / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
//Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Biological Markers; 0/Homeodomain Proteins; 0/Maf Transcription Factors, Large; 0/Mafa protein, mouse; 0/Nerve Tissue Proteins; 0/Neurog3 protein, mouse; 0/Trans-Activators; 0/Transcription Factors; 0/pancreatic and duodenal homeobox 1 protein; 11061-68-0/Insulin
Comments/Corrections
Comment In:
Nature. 2008 Oct 2;455(7213):604-5   [PMID:  18833266 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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