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Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation

Author

Listed:
  • Yuval Dor

    (Harvard University)

  • Juliana Brown

    (Harvard University)

  • Olga I. Martinez

    (Harvard University)

  • Douglas A. Melton

    (Harvard University)

Abstract

How tissues generate and maintain the correct number of cells is a fundamental problem in biology. In principle, tissue turnover can occur by the differentiation of stem cells, as is well documented for blood, skin and intestine, or by the duplication of existing differentiated cells. Recent work on adult stem cells has highlighted their potential contribution to organ maintenance and repair. However, the extent to which stem cells actually participate in these processes in vivo is not clear. Here we introduce a method for genetic lineage tracing to determine the contribution of stem cells to a tissue of interest. We focus on pancreatic β-cells, whose postnatal origins remain controversial. Our analysis shows that pre-existing β-cells, rather than pluripotent stem cells, are the major source of new β-cells during adult life and after pancreatectomy in mice. These results suggest that terminally differentiated β-cells retain a significant proliferative capacity in vivo and cast doubt on the idea that adult stem cells have a significant role in β-cell replenishment.

Suggested Citation

  • Yuval Dor & Juliana Brown & Olga I. Martinez & Douglas A. Melton, 2004. "Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation," Nature, Nature, vol. 429(6987), pages 41-46, May.
    • Handle: RePEc:nat:nature:v:429:y:2004:i:6987:d:10.1038_nature02520
    DOI: 10.1038/nature02520
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    Cited by:

    1. Hiroto Sugawara & Junta Imai & Junpei Yamamoto & Tomohito Izumi & Yohei Kawana & Akira Endo & Masato Kohata & Junro Seike & Haremaru Kubo & Hiroshi Komamura & Yuichiro Munakata & Yoichiro Asai & Shini, 2023. "A highly sensitive strategy for monitoring real-time proliferation of targeted cell types in vivo," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Dan Frumkin & Adam Wasserstrom & Shai Kaplan & Uriel Feige & Ehud Shapiro, 2005. "Genomic Variability within an Organism Exposes Its Cell Lineage Tree," PLOS Computational Biology, Public Library of Science, vol. 1(5), pages 1-13, October.
    3. Deborah A Striegel & Manami Hara & Vipul Periwal, 2015. "The Beta Cell in Its Cluster: Stochastic Graphs of Beta Cell Connectivity in the Islets of Langerhans," PLOS Computational Biology, Public Library of Science, vol. 11(8), pages 1-29, August.
    4. Andhira Vieira & Bastien Vergoni & Monica Courtney & Noémie Druelle & Elisabet Gjernes & Biljana Hadzic & Fabio Avolio & Tiziana Napolitano & Sergi Navarro Sanz & Ahmed Mansouri & Patrick Collombat, 2018. "Neurog3 misexpression unravels mouse pancreatic ductal cell plasticity," PLOS ONE, Public Library of Science, vol. 13(8), pages 1-22, August.

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