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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Qiao Zhou & Juliana Brown & Andrew Kanarek & Jayaraj Rajagopal & Douglas A. Melton, 2008. "In vivo reprogramming of adult pancreatic exocrine cells to β-cells," Nature, Nature, vol. 455(7213), pages 627-632, October.
    • Handle: RePEc:nat:nature:v:455:y:2008:i:7213:d:10.1038_nature07314
    DOI: 10.1038/nature07314
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    Cited by:

    1. Shakti Dahiya & Mohamed Saleh & Uylissa A. Rodriguez & Dhivyaa Rajasundaram & Jorge R. Arbujas & Arian Hajihassani & Kaiyuan Yang & Anuradha Sehrawat & Ranjeet Kalsi & Shiho Yoshida & Krishna Prasadan, 2024. "Acinar to β-like cell conversion through inhibition of focal adhesion kinase," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Joan Teichenne & Meritxell Morró & Alba Casellas & Veronica Jimenez & Noelia Tellez & Adrien Leger & Fatima Bosch & Eduard Ayuso, 2015. "Identification of miRNAs Involved in Reprogramming Acinar Cells into Insulin Producing Cells," PLOS ONE, Public Library of Science, vol. 10(12), pages 1-20, December.
    3. Xingting Guo & Chenhui Wang & Yongchao Zhang & Ruxue Wei & Rongwen Xi, 2024. "Cell-fate conversion of intestinal cells in adult Drosophila midgut by depleting a single transcription factor," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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