title: Dedifferentiation of committed epithelial cells into stem cells in vivo.
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.
authors.affiliation: 1] Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA [2] Departments of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts 02114, USA [3] Department of Internal Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA [4] Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA.
authors.forename: Purushothama Rao
authors.initials: PR
authors.lastname: Tata
authors.forename: Hongmei
authors.initials: H
authors.lastname: Mou
authors.forename: Ana
authors.initials: A
authors.lastname: Pardo-Saganta
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.forename: Mythili
authors.initials: M
authors.lastname: Prabhu
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Law
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vinarsky
authors.forename: Josalyn L
authors.initials: JL
authors.lastname: Cho
authors.forename: Sylvie
authors.initials: S
authors.lastname: Breton
authors.forename: Amar
authors.initials: A
authors.lastname: Sahay
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Medoff
authors.forename: Jayaraj
authors.initials: J
authors.lastname: Rajagopal
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D054337:Cell Dedifferentiation; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D004318:Doxycycline / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects; D005260:Female; D008297:Male; D008822:Mice, Transgenic; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D004318:Doxycycline