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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state
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Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state

机译：正常和赘生性非干细胞可自发转变为干样状态

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摘要

Current models of stem cell biology assume that normal and neoplastic stem cells reside at the apices of hierarchies and differentiate into nonstem progeny in a unidirectional manner. Here we identify a subpopulation of basal-like human mammary epithelial cells that departs from that assumption, spontaneously dediffer-entiating into stem-like cells. Moreover, oncogenic transformation enhances the spontaneous conversion, so that nonstem cancer cells give rise to cancer stem cell (CSC)-like cells in vitro and in vivo. We further show that the differentiation state of normal cells-of-origin is a strong determinant of posttransformation behavior. These findings demonstrate that normal and CSC-like cells can arise de novo from more differentiated cell types and that hierarchical models of mammary stem cell biology should encompass bidirectional interconver-sions between stem and nonstem compartments. The observed plasticity may allow derivation of patient-specific adult stem cells without genetic manipulation and holds important implications for therapeutic strategies to eradicate cancer.
机译：当前的干细胞生物学模型假设正常和赘生性干细胞位于层次的顶端，并以单向方式分化为非干后代。在这里，我们确定了与该假设背离的基底样人乳腺上皮细胞的亚群，自发地分化为干样细胞。此外，致癌转化增强了自发转化，从而非干癌细胞在体外和体内都产生了癌干细胞（CSC）样细胞。我们进一步表明，正常来源细胞的分化状态是转化后行为的强力决定因素。这些发现表明正常和CSC样细胞可以从分化程度更高的细胞类型中重新产生，并且乳腺干细胞生物学的分层模型应涵盖干细胞和非干细胞之间的双向互换。观察到的可塑性可能无需基因操作即可衍生出患者特异性的成年干细胞，并且对根除癌症的治疗策略具有重要意义。

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    Christine L. Chaffer; Ines Brueckmann; Christina Scheel; Alicia J. Kaestli; Paul A. Wiggins; Leonardo O. Rodrigues; Mary Brooks; Ferenc Reinhardt; Ying Su; Kornelia Polyak; Lisa M. Arendt; Charlotte Kuperwasser; Brian Bierie; Robert A. Weinberg;

  • 作者单位

    Whitehead Institute for Biomedical Research, Cambridge, MA 02142,Ludwig MIT Center for Molecular Oncology, Cambridge, MA 02139;

    Whitehead Institute for Biomedical Research, Cambridge, MA 02142;

    Whitehead Institute for Biomedical Research, Cambridge, MA 02142,Ludwig MIT Center for Molecular Oncology, Cambridge, MA 02139;

    Whitehead Institute for Biomedical Research, Cambridge, MA 02142;

    Whitehead Institute for Biomedical Research, Cambridge, MA 02142;

    Whitehead Institute for Biomedical Research, Cambridge, MA 02142,Ludwig MIT Center for Molecular Oncology, Cambridge, MA 02139;

    Whitehead Institute for Biomedical Research, Cambridge, MA 02142,Ludwig MIT Center for Molecular Oncology, Cambridge, MA 02139;

    Whitehead Institute for Biomedical Research, Cambridge, MA 02142,Ludwig MIT Center for Molecular Oncology, Cambridge, MA 02139;

    Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115;

    Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115;

    Ludwig MIT Center for Molecular Oncology, Cambridge, MA 02139,Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111;

    Department of Anatomy and Cellular Biology, Sackler School, Tufts University School of Medicine, Boston, MA 02111,Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111;

    Whitehead Institute for Biomedical Research, Cambridge, MA 02142,Ludwig MIT Center for Molecular Oncology, Cambridge, MA 02139;

    Whitehead Institute for Biomedical Research, Cambridge, MA 02142,Ludwig MIT Center for Molecular Oncology, Cambridge, MA 02139,Department of Biology,Massachusetts Institute of Technology, Cambridge, MA 02139;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    breast cancer; dedifferentiation;

    机译：乳腺癌;去分化;

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