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Parent stem cells can serve as niches for their daughter cells

机译：亲代干细胞可以充当子代细胞的利基

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摘要

Stem cells integrate inputs from multiple sources. Stem cell niches provide signals that promote stem cell maintenance(1,2), while differentiated daughter cells are known to provide feedback signals to regulate stem cell replication and differentiation(3-6). Recently, stem cells have been shown to regulate themselves using an autocrine mechanism(7). The existence of a 'stem cell niche' was first postulated by Schofield in 1978 to define local environments necessary for the maintenance of haematopoietic stem cells1. Since then, an increasing body of work has focused on defining stem cell niches(1-6). Yet little is known about how progenitor cell and differentiated cell numbers and proportions are maintained. In the airway epithelium, basal cells function as stem/progenitor cells that can both self-renew and produce differentiated secretory cells and ciliated cells(8,9). Secretory cells also act as transit-amplifying cells that eventually differentiate into post-mitotic ciliated cells(9,10). Here we describe a mode of cell regulation in which adult mammalian stem/progenitor cells relay a forward signal to their own progeny. Surprisingly, this forward signal is shown to be necessary for daughter cell maintenance. Using a combination of cell ablation, lineage tracing and signalling pathway modulation, we show that airway basal stem/progenitor cells continuously supply a Notch ligand to their daughter secretory cells. Without these forward signals, the secretory progenitor cell pool fails to be maintained and secretory cells execute a terminal differentiation program and convert into ciliated cells. Thus, a parent stem/progenitor cell can serve as a functional daughter cell niche.
机译：干细胞整合来自多个来源的输入。干细胞壁ches提供促进干细胞维持的信号（1,2），而分化的子细胞可提供反馈信号以调节干细胞的复制和分化（3-6）。近来，干细胞已显示出利用自分泌机制来调节自身功能（7）。 1978年，Schofield首先提出了“干细胞小生境”的存在，以定义维持造血干细胞所必需的局部环境。从那时起，越来越多的工作集中在定义干细胞壁ches上（1-6）。对于如何维持祖细胞和分化的细胞数量和比例知之甚少。在气道上皮中，基础细胞起干/祖细胞的作用，既可以自我更新又可以产生分化的分泌细胞和纤毛细胞（8,9）。分泌细胞还可以作为转运扩增细胞，最终分化为有丝分裂后纤毛细胞（9,10）。在这里，我们描述了一种细胞调节模式，其中成年哺乳动物干/祖细胞将正向信号传递给它们自己的后代。出人意料的是，该前向信号显示为子电池维护所必需。使用细胞消融，沿袭追踪和信号通路调制的组合，我们表明，气道基底干/祖细胞不断向其子代分泌细胞提供Notch配体。没有这些前向信号，分泌祖细胞池将无法维持，分泌细胞执行终末分化程序并转化为纤毛细胞。因此，亲本干/祖细胞可以用作功能性子细胞小生境。

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  • 来源
    《Nature》 |2015年第7562期|597-601|共5页
  • 作者

    Pardo-Saganta Ana; Tata Purushothama Rao; Law Brandon M.; Saez Borja; Chow Ryan Dz-Wei; Prabhu Mythili; Gridley Thomas; Rajagopal Jayaraj;

  • 作者单位

    Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA|Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA|Massachusetts Gen Hosp, Dept Pediat, Pulm & Crit Care Unit, Boston, MA 02114 USA|Harvard Stem Cell Inst, Cambridge, MA 02138 USA;

    Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA|Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA|Massachusetts Gen Hosp, Dept Pediat, Pulm & Crit Care Unit, Boston, MA 02114 USA|Harvard Stem Cell Inst, Cambridge, MA 02138 USA;

    Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA|Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA|Massachusetts Gen Hosp, Dept Pediat, Pulm & Crit Care Unit, Boston, MA 02114 USA|Harvard Stem Cell Inst, Cambridge, MA 02138 USA;

    Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA|Harvard Stem Cell Inst, Cambridge, MA 02138 USA|Harvard Univ, Stem Cell & Regenerat Biol Dept, Cambridge, MA 02138 USA;

    Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA|Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA|Massachusetts Gen Hosp, Dept Pediat, Pulm & Crit Care Unit, Boston, MA 02114 USA|Harvard Stem Cell Inst, Cambridge, MA 02138 USA;

    Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA|Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA|Massachusetts Gen Hosp, Dept Pediat, Pulm & Crit Care Unit, Boston, MA 02114 USA|Harvard Stem Cell Inst, Cambridge, MA 02138 USA;

    Maine Med Ctr, Res Inst, Ctr Mol Med, Scarborough, ME 04074 USA;

    Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA|Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA|Massachusetts Gen Hosp, Dept Pediat, Pulm & Crit Care Unit, Boston, MA 02114 USA|Harvard Stem Cell Inst, Cambridge, MA 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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