Dedifferentiation of committed epithelial cells into stem cells in vivo.

Published

Journal Article

Cellular plasticity contributes to the regenerative capacity of plants, invertebrates, teleost fishes and amphibians. In vertebrates, differentiated cells are known to revert into replicating progenitors, but these cells do not persist as stable stem cells. Here we present evidence that differentiated airway epithelial cells can revert into stable and functional stem cells in vivo. After the ablation of airway stem cells, we observed a surprising increase in the proliferation of committed secretory cells. Subsequent lineage tracing demonstrated that the luminal secretory cells had dedifferentiated into basal stem cells. Dedifferentiated cells were morphologically indistinguishable from stem cells and they functioned as well as their endogenous counterparts in repairing epithelial injury. Single secretory cells clonally dedifferentiated into multipotent stem cells when they were cultured ex vivo without basal stem cells. By contrast, direct contact with a single basal stem cell was sufficient to prevent secretory cell dedifferentiation. In analogy to classical descriptions of amphibian nuclear reprogramming, the propensity of committed cells to dedifferentiate is inversely correlated to their state of maturity. This capacity of committed cells to dedifferentiate into stem cells may have a more general role in the regeneration of many tissues and in multiple disease states, notably cancer.

Full Text

Duke Authors

Cited Authors

  • Tata, PR; Mou, H; Pardo-Saganta, A; Zhao, R; Prabhu, M; Law, BM; Vinarsky, V; Cho, JL; Breton, S; Sahay, A; Medoff, BD; Rajagopal, J

Published Date

  • November 6, 2013

Published In

Volume / Issue

  • 503 / 7475

Start / End Page

  • 218 - 223

PubMed ID

  • 24196716

Pubmed Central ID

  • 24196716

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature12777

Language

  • eng