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,Jayaraj Rajagopal +11 more
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TLDR
Evidence is presented that differentiated airway epithelial cells can revert into stable and functional stem cells in vivo, and 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.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.read more
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Evolution of the Cancer Stem Cell Model
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Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function.
Brigid L.M. Hogan,Christina E. Barkauskas,Harold A. Chapman,Jonathan A. Epstein,Rajan Jain,Connie C. W. Hsia,Laura E. Niklason,Elizabeth A. Calle,Andrew V. Le,Scott H. Randell,Jason R. Rock,Melinda Snitow,Matthew F. Krummel,Barry R. Stripp,Thiennu H. Vu,Eric S. White,Jeffrey A. Whitsett,Edward E. Morrisey +17 more
TL;DR: The multiple stem/progenitor populations in different regions of the adult lung, the plasticity of their behavior in injury models, and molecular pathways that support homeostasis and repair are highlighted.
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