Transit-amplifying cells orchestrate stem cell activity and tissue regeneration.

Transit-amplifying cells orchestrate stem cell activity and tissue regeneration.
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DOI:
10.1016/j.cell.2014.02.057
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发表时间:
2014-05-08
期刊:
影响因子:
64.5
通讯作者:
Fuchs E
Fuchs E
中科院分区:
生物学1区
文献类型:
--
作者:
Hsu YC;Li L;Fuchs E

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传递放大细胞(TAC)是组织再生的早期中间体。在这里,使用毛囊(HF)作为范例,我们表明,新兴的TAC构成了一个信号中心,协调组织生长。当引发的干细胞(SC)产生TAC时,静止的SC仅在TAC形成并开始表达Sonic Hedgehog(SHH)后增殖。TAC的产生是独立的自分泌SHH,但他们的池减少,如果他们不能产生it.We跟踪这一矛盾的两个直接作用SHH:促进静止SC增殖和调节真皮因子,斯托克TAC扩张。静止SC对SHH信号的特殊敏感性是其GAS1的高表达。在没有来自静止SC的足够输入的情况下,用于下一毛发周期的引发SC的补充受到损害,从而延迟再生并最终导致再生失败。我们的研究结果揭示了TACs作为SC生态位组分的短暂但不可或缺的整合剂,并揭示了启动和静止SC群体对组织再生的有趣的相互依赖性。
Transit-amplifying cells (TACs) are an early intermediate in tissue regeneration. Here, using hair follicles (HFs) as paradigm, we show that emerging TACs constitute a signaling center that orchestrates tissue growth. While primed stem cells (SCs) generate TACs, quiescent-SCs only proliferate after TACs form and begin expressing Sonic Hedgehog (SHH). TAC generation is independent of autocrine SHH, but their pool wanes if they can’t produce it. We trace this paradox to two direct actions of SHH: promoting quiescent-SC proliferation and regulating dermal factors that stoke TAC expansion. Ingrained within quiescent-SC’s special sensitivity to SHH signaling is their high expression of GAS1. Without sufficient input from quiescent-SCs, replenishment of primed-SCs for the next hair cycle is compromised, delaying regeneration and eventually leading to regeneration failure. Our findings unveil TACs as transient but indispensable integrator of SC niche components and reveal an intriguing interdependency of primed and quiescent SC populations on tissue regeneration.
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发表时间: 2013-09-05
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影响因子: 23.9
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