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Dedifferentiation of committed epithelial cells into stem cells in vivo

机译：体内定型上皮细胞向干细胞去分化

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摘要

通过对小鼠进行活体世系追踪和使用筛选的培养细胞，Jayaraj Rajagopal及同事研究了小鼠气管上皮中分化的分泌细胞"去分化"成对成年气管起干细胞作用的基细胞的能力。他们的发现表明，定型细胞类型向干细胞的"去分化"对于高等脊椎动物在不同器官中和受伤情形下的再生能力可能具有更为普遍的贡献。%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 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.
机译：通过对小鼠进行活体世系追踪和使用筛选的培养细胞，Jayaraj Rajagopal及同事研究了小鼠气管上皮中分化的分泌细胞"去分化"成对成年气管起干细胞作用的基细胞的能力。他们的发现表明，定型细胞类型向干细胞的"去分化"对于高等脊椎动物在不同器官中和受伤情形下的再生能力可能具有更为普遍的贡献。%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 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.

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  • 来源
    《Nature》 |2013年第7475期|218-223153|共7页
  • 作者

    Purushothama Rao Tata; Hongmei Mou; Ana Pardo-Saganta; Rui Zhao; Mvthili Prabhu; Brandon M. Law; Vladimir Vinarsky; Josalyn L. Cho; Sylvie Breton; Amar Sahay; Benjamin D. Medoff; Jayaraj Rajagopal;

  • 作者单位

    Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA,Departments of Pediatrics, Massachusetts General Hospital, Boston,Massachusetts 02114, USA,Department of Internal Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA,Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA;

    Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA,Departments of Pediatrics, Massachusetts General Hospital, Boston,Massachusetts 02114, USA,Department of Internal Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA,Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA;

    Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA,Departments of Pediatrics, Massachusetts General Hospital, Boston,Massachusetts 02114, USA,Department of Internal Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA,Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA;

    Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA,Departments of Pediatrics, Massachusetts General Hospital, Boston,Massachusetts 02114, USA,Department of Internal Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA,Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA;

    Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA,Departments of Pediatrics, Massachusetts General Hospital, Boston,Massachusetts 02114, USA,Department of Internal Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA,Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA;

    Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA,Departments of Pediatrics, Massachusetts General Hospital, Boston,Massachusetts 02114, USA,Department of Internal Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA,Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA;

    Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA,Departments of Pediatrics, Massachusetts General Hospital, Boston,Massachusetts 02114, USA,Department of Internal Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA,Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA;

    Department of Internal Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA,Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA;

    Center for Systems Biology, Program in Membrane Biology and Nephrology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02214, USA;

    Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA,Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA,Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02215, USA;

    Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA,Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA;

    Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA,Departments of Pediatrics, Massachusetts General Hospital, Boston,Massachusetts 02114, USA,Department of Internal Medicine, Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA,Harvard Stem Cell Institute, Cambridge, Massachusetts 02138, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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