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Germ-layer and lineage-restricted stem/progenitors regenerate the mouse digit tip

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  • Yuval Rinkevich

    (Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine
    Present address: Institute for Stem Cell Biology and Regenerative Medicine, Lorry I. Lokey Research Building, Stanford University, Stanford, California 94028, USA.)

  • Paul Lindau

    (Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine)

  • Hiroo Ueno

    (Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine)

  • Michael T. Longaker

    (Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine
    Hagey Laboratory for Pediatric Regenerative Medicine, Plastic and Reconstructive Surgery, Stanford University School of Medicine)

  • Irving L. Weissman

    (Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine
    Ludwig Center for Cancer Stem Cell Research, Stanford University, Stanford)

Abstract

The regrowth of amputated limbs and the distal tips of digits represent models of tissue regeneration in amphibians, fish and mice. For decades it had been assumed that limb regeneration derived from the blastema, an undifferentiated pluripotent cell population thought to be derived from mature cells via dedifferentiation. Here we show that a wide range of tissue stem/progenitor cells contribute towards the restoration of the mouse distal digit. Genetic fate mapping and clonal analysis of individual cells revealed that these stem cells are lineage restricted, mimicking digit growth during development. Transplantation of cyan-fluorescent-protein-expressing haematopoietic stem cells, and parabiosis between genetically marked mice, confirmed that the stem/progenitor cells are tissue resident, including the cells involved in angiogenesis. These results, combined with those from appendage regeneration in other vertebrate subphyla, collectively demonstrate that tissue stem cells rather than pluripotent blastema cells are an evolutionarily conserved cellular mode for limb regeneration after amputation.

Suggested Citation

  • Yuval Rinkevich & Paul Lindau & Hiroo Ueno & Michael T. Longaker & Irving L. Weissman, 2011. "Germ-layer and lineage-restricted stem/progenitors regenerate the mouse digit tip," Nature, Nature, vol. 476(7361), pages 409-413, August.
    • Handle: RePEc:nat:nature:v:476:y:2011:i:7361:d:10.1038_nature10346
    DOI: 10.1038/nature10346
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    Cited by:

    1. Ariel C. Vonk & Xiaofan Zhao & Zheyu Pan & Megan L. Hudnall & Conrad G. Oakes & Gabriela A. Lopez & Sarah C. Hasel-Kolossa & Alexander W. C. Kuncz & Sasha B. Sengelmann & Darian J. Gamble & Thomas P. , 2023. "Single-cell analysis of lizard blastema fibroblasts reveals phagocyte-dependent activation of Hedgehog-responsive chondrogenesis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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