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Dedifferentiation of committed epithelial cells into stem cells in vivo

2013; Nature Portfolio; Volume: 503; Issue: 7475 Linguagem: Inglês

10.1038/nature12777

1476-4687

Purushothama Rao Tata, Hongmei Mou, Ana Pardo–Saganta, Rui Zhao, Mythili Prabhu, Brandon M. Law, Vladimir Vinarsky, Christina Schofield, Sylvie Breton, Amar Sahay, Benjamin D. Medoff, Jayaraj Rajagopal,

Epigenetics and DNA Methylation

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. Using in vivo lineage tracing in mice and sorted cells in culture, the ability of stably committed cells to dedifferentiate into basal stem cells in the mouse trachea is investigated: the findings suggest that the dedifferentiation of committed cell types into stem cells may contribute generally to regeneration in higher vertebrates in different organ and injury contexts. Using in vivo lineage tracing in mice and sorted cells in culture, Jayaraj Rajagopal and colleagues have investigated the ability of differentiated secretory cells in mouse airway epithelia to dedifferentiate into basal cells that function as stem cells for the adult airway. Their findings suggest that the dedifferentiation of committed cell types into stem cells may contribute more generally to the regenerative capacity of higher vertebrates in different organs and injury contexts.