Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA.
Cell Stem Cell. 2013 Sep 5;13(3):314-27. doi: 10.1016/j.stem.2013.06.018.
In adult skin, self-renewing, undifferentiated hair follicle stem cells (HF-SCs) reside within a specialized niche, where they spend prolonged times as a single layer of polarized, quiescent epithelial cells. When sufficient activating signals accumulate, HF-SCs become mobilized to fuel tissue regeneration and hair growth. Here, we show that architectural organization of the HF-SC niche by transcription factor LHX2 plays a critical role in HF-SC behavior. Using genome-wide chromatin and transcriptional profiling of HF-SCs in vivo, we show that LHX2 directly transactivates genes that orchestrate cytoskeletal dynamics and adhesion. Conditional ablation of LHX2 results in gross cellular disorganization and HF-SC polarization within the niche. LHX2 loss leads to a failure to maintain HF-SC quiescence and hair anchoring, as well as progressive transformation of the niche into a sebaceous gland. These findings suggest that niche organization underlies the requirement for LHX2 in hair follicle structure and function.
在成人皮肤中，自我更新的、未分化的毛囊干细胞（HF-SCs）位于一个专门的龛位内，在那里它们作为一层极化的静止上皮细胞长时间存在。当积累了足够的激活信号时，HF-SCs 就会被动员起来为组织再生和毛发生长提供燃料。在这里，我们表明转录因子 LHX2 对 HF-SC 龛位的结构组织起着关键作用。通过对体内 HF-SC 的全基因组染色质和转录谱进行分析，我们表明 LHX2 可以直接激活协调细胞骨架动态和黏附的基因。条件性敲除 LHX2 会导致细胞内的严重紊乱和 HF-SC 在龛位内的极化。LHX2 的缺失导致 HF-SC 静止和毛锚固的维持失败，以及龛位逐渐转化为皮脂腺。这些发现表明，龛位组织是 LHX2 维持毛囊结构和功能所必需的。
