Dedifferentiation of committed epithelial cells into stem cells in vivo

Purushothama Rao Tata, Hongmei Mou, Ana Pardo-Saganta, Rui Zhao, Mythili Prabhu, Brandon M. Law, Vladimir Vinarsky, Josalyn L. Cho, Sylvie Breton, Amar Sahay, Benjamin D. Medoff and Jayaraj Rajagopal ()
Additional contact information
Purushothama Rao Tata: Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA
Hongmei Mou: Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA
Ana Pardo-Saganta: Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA
Rui Zhao: Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA
Mythili Prabhu: Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA
Brandon M. Law: Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA
Vladimir Vinarsky: Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA
Josalyn L. Cho: Pulmonary and Critical Care Unit, Massachusetts General Hospital
Sylvie Breton: Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School
Amar Sahay: Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA
Benjamin D. Medoff: Pulmonary and Critical Care Unit, Massachusetts General Hospital
Jayaraj Rajagopal: Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA

Nature, 2013, vol. 503, issue 7475, 218-223

Abstract: Abstract 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.

Date: 2013
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DOI: 10.1038/nature12777

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