Publication Date:
2008-08-30
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Qiao -- Brown, Juliana -- Kanarek, Andrew -- Rajagopal, Jayaraj -- Melton, Douglas A -- Howard Hughes Medical Institute/ -- England -- Nature. 2008 Oct 2;455(7213):627-32. doi: 10.1038/nature07314. Epub 2008 Aug 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18754011" target="_blank"〉PubMed〈/a〉
Keywords:
Aging/physiology
;
Animals
;
Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism
;
Biomarkers/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
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
