过渡扩增细胞协调干细胞活动和组织再生。
Transit-amplifying cells orchestrate stem cell activity and tissue regeneration.
机构信息
Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
出版信息
Cell. 2014 May 8;157(4):935-49. doi: 10.1016/j.cell.2014.02.057.
Transit-amplifying cells (TACs) are an early intermediate in tissue regeneration. Here, using hair follicles (HFs) as a paradigm, we show that emerging TACs constitute a signaling center that orchestrates tissue growth. Whereas 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 the TAC pool wanes if they can't produce SHH. 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 SCs' 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 integrators of SC niche components and reveal an intriguing interdependency of primed and quiescent SC populations on tissue regeneration.
过渡扩增细胞（TACs）是组织再生的早期中间产物。在这里，我们以毛囊（HFs）为例，表明新兴的 TAC 构成了一个信号中心，协调组织生长。虽然有启动的干细胞（SCs）产生 TACs，但静止的SCs 仅在 TAC 形成并开始表达 Sonic Hedgehog（SHH）后才增殖。TAC 的产生不依赖于自分泌的 SHH，但如果 TAC 池不能产生 SHH，其数量就会减少。我们将这种矛盾追溯到 SHH 的两个直接作用：促进静止-SC 增殖和调节刺激 TAC 扩张的真皮因子。在静止 SCs 对 SHH 信号的特殊敏感性中，有其高表达的 GAS1。如果没有静止 SCs 的足够输入，下一个毛发周期的启动 SCs 的补充就会受到影响，从而延迟再生，最终导致再生失败。我们的发现揭示了 TACs 作为 SC 生态位成分的短暂但不可或缺的整合者，并揭示了启动和静止 SC 群体对组织再生的有趣的相互依存关系。
Zotero 插件