Dedifferentiation of committed epithelial cells into stem cells in vivo.
Dedifferentiation of committed epithelial cells into stem cells in vivo.
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作者：
细胞可塑性有助于植物、无脊椎动物、硬骨鱼和两栖动物的再生能力。在脊椎动物中，已知分化的细胞可以恢复为复制祖细胞，但这些细胞不能作为稳定的干细胞持续存在。我们现在提出的证据表明，分化的气道上皮细胞可以在体内恢复为稳定和功能性干细胞。消融气道干细胞后，我们观察到定向分泌细胞增殖的惊人增加。随后的谱系追踪表明，腔分泌细胞已去分化为基底干细胞。去分化细胞在形态上与干细胞难以区分，它们的功能与内源性对应物一样，可以修复上皮损伤。事实上，单个分泌细胞克隆去分化成多能干细胞时，他们离体培养没有基础干细胞。相反，与单个基底干细胞直接接触足以防止分泌细胞去分化。与两栖动物核重编程的经典描述类似，定向细胞去分化的倾向与其成熟状态呈负相关。这种定向细胞去分化为干细胞的能力可能在许多组织的再生和多种疾病状态中发挥更普遍的作用，特别是癌症。
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.
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DOI：
10.1126/science.1189992
发表时间：
2010-07-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Goldstein AS;Huang J;Guo C;Garraway IP;Witte ON
通讯作者：
Witte ON
影响因子：
21.3
作者：
通讯作者：
--
肿瘤基因对神经元和星形胶质细胞的去分化会在小鼠中诱导神经胶质瘤。
DOI：
10.1126/science.1226929
发表时间：
2012-11-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Friedmann-Morvinski D;Bushong EA;Ke E;Soda Y;Marumoto T;Singer O;Ellisman MH;Verma IM
通讯作者：
Verma IM
影响因子：
64.5
作者：
Hsu YC;Pasolli HA;Fuchs E
通讯作者：
Fuchs E
影响因子：
64.5
作者：
Schwitalla, Sarah;Fingerle, Alexander A.;Greten, Florian R.
通讯作者：
Greten, Florian R.