Dedifferentiation of committed epithelial cells into stem cells in vivo

By P. Tata, H. Mou, A. Pardo-Saganta, Rui Zhao, Mythili Prabhu, Brandon M. Law, V. Vinarský, Josalyn L. Cho, S. Breton, Amar Sahay and 2 more. Nature, 2013

644 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/941f2b55b7669715a09c27bc1af5584a1b1acb87

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. Fabian J Theis
2. H. Schiller
3. Marius Lange
4. Volker Bergen
5. Dana Pe'er
6. Manu N. Setty
7. J. Dick
8. J. Rock

In Pulmonary and Respiratory Medicine

1. J. Rock
2. E. Morrisey
3. B. Stripp
4. B. Hogan
5. C. E. Barkauskas
6. S. Randell

Citations in the corpus

• CellRank for directed single-cell fate mapping (2020, positive): “A high degree of plasticity between epithelial cell types has been observed when homeostasis is perturbed and the tissue environment changes, including injury-induced reprogramming of differentiated cell types to bona fide long-lived stem cells in the lung 54 and other organs 55 .”
• Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function (2014, background): “Recent studies in the human lung have described a powerful non-invasive lineage tracing methodology for addressing the potential of individual airway progenitor cells to self-renew and differentiate (Teixeira et al., 2013).”
• Evolution of the cancer stem cell model. (2014, background): “Normal tissue stem cells can also ‘‘dedifferentiate’’ into a more primitive state when normal tissue homeostasis is perturbed, for example during transplantation procedures or following stem cell ablation (Rinkevich et al., 2011; Tata et al., 2013; Van Keymeulen et al., 2011).”