In vivo reprogramming of adult pancreatic exocrine cells to β-cells

Qiao Zhou, Juliana Brown, Andrew Kanarek, Jayaraj Rajagopal and Douglas A. Melton ()
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Qiao Zhou: Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
Juliana Brown: Children’s Hospital, Boston, Harvard Medical School, Harvard Stem Cell Institute, 300 Longwood Avenue, Boston, Massachusetts 02115-5724, USA
Andrew Kanarek: Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
Jayaraj Rajagopal: Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
Douglas A. Melton: Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA

Nature, 2008, vol. 455, issue 7213, 627-632

Abstract: Abstract 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 β-cells. The induced β-cells are indistinguishable from endogenous islet β-cells in size, shape and ultrastructure. They express genes essential for β-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.

Date: 2008
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DOI: 10.1038/nature07314

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