Journal article
Dedifferentiation of committed epithelial cells into stem cells in vivo
Nature (London), Vol.503(7475), pp.218-223
11/14/2013
DOI: 10.1038/nature12777
PMCID: PMC4035230
PMID: 24196716
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. We now present evidence that differentiated airway epithelial cells can revert into stable and functional stem cells
in vivo.
Following 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 to repair epithelial injury. Indeed, single secretory cells clonally dedifferentiated into multipotent stem cells when they were cultured
ex vivo
without basal stem cells. In 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 was inversely correlated to their state of maturity. This capacity of committed cells to dedifferentiate into stem cells may play a more general role in the regeneration of many tissues and in multiple disease states, notably cancer.
Details
- Title: Subtitle
- Dedifferentiation of committed epithelial cells into stem cells in vivo
- Creators
- Purushothama Rao Tata - Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA02114, USAHongmei Mou - Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA02114, USAAna Pardo-Saganta - Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA02114, USARui Zhao - Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA02114, USAMythili Prabhu - Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA02114, USABrandon M Law - Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA02114, USAVladimir Vinarsky - Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA02114, USAJosalyn L Cho - Department of Internal Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, MA 02114, USASylvie Breton - Center for Systems Biology, Program in Membrane Biology/Nephrology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02214Amar Sahay - Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA02114, USABenjamin D Medoff - Department of Internal Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, MA 02114, USAJayaraj Rajagopal - Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA02114, USA
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.503(7475), pp.218-223
- DOI
- 10.1038/nature12777
- PMID
- 24196716
- PMCID
- PMC4035230
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Language
- English
- Date published
- 11/14/2013
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984094322802771
Metrics
26 Record Views