Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development.

Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development.
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SIX2定义并调节整个哺乳动物肾脏发育中的多方自我更新肾祖先种群。

DOI:
10.1016/j.stem.2008.05.020
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发表时间:
2008-08-07
期刊:
影响因子:
23.9
通讯作者:
McMahon, Andrew P.
McMahon, Andrew P.
中科院分区:
医学1区
文献类型:
--
作者:
Kobayashi, Akio;Valerius, M. Todd;Mugford, Joshua W.;Carroll, Thomas J.;Self, Michelle;Oliver, Guillermo;McMahon, Andrew P.

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肾单位是肾脏的基本功能单位,在肾脏器官发生过程中从间充质祖细胞群体中重复产生。在这个旷日持久的发育过程中,这个池中的哪些细胞产生了肾单位,以及多个肾单位谱系是如何形成的,目前尚不清楚。我们证明,表达SIX2的CAP间充质细胞代表了一个多能的肾单位祖细胞群体。在肾发生的各个阶段,表达SIX2的细胞可分化为肾单位主体的所有细胞类型。肾脏发育初期表达SIX2的肾祖细胞的脉冲标记表明,表达SIX2的群体是通过自我更新来维持的。克隆分析表明,至少有一些表达SIX2的细胞是多能的,参与了肾单位的多个结构域。此外,SIX2发挥细胞自主功能以维持祖细胞状态,因为缺乏SIX2活性的帽间充质细胞有助于异位肾小管,这一机制依赖于Wnt9b诱导信号。综上所述,我们的观察表明,SIX2活性细胞自主调节多潜能肾单位祖细胞群体。
Nephrons, the basic functional units of the kidney, are generated repetitively during kidney organogenesis from a mesenchymal progenitor population. Which cells within this pool give rise to nephrons and how multiple nephron lineages form during this protracted developmental process is unclear. We demonstrate that the Six2-expressing cap mesenchyme represents a multipotent nephron progenitor population. Six2-expressing cells give rise to all cell-types of the main body of the nephron, during all stages of nephrogenesis. Pulse labeling of Six2-expressing nephron progenitors at the onset of kidney development suggests that the Six2-expressing population is maintained by self-renewal. Clonal analysis indicates that at least some Six2-expressing cells are multipotent, contributing to multiple domains of the nephron. Furthermore, Six2 functions cell-autonomously to maintain a progenitor cell status, as cap mesenchyme cells lacking Six2 activity contribute to ectopic nephron tubules, a mechanism dependent on a Wnt9b inductive signal. Taken together, our observations suggest that Six2 activity cell-autonomously regulates a multipotent nephron progenitor population.
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