Architectural niche organization by LHX2 is linked to hair follicle stem cell function.
Architectural niche organization by LHX2 is linked to hair follicle stem cell function.
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DOI：
10.1016/j.stem.2013.06.018
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发表时间：
2013-09-05
期刊：
影响因子：
23.9
通讯作者：
Fuchs E
中科院分区：
文献类型：
--
作者：
Folgueras AR;Guo X;Pasolli HA;Stokes N;Polak L;Zheng D;Fuchs E
在成人皮肤中，自我更新的、未分化的毛囊干细胞（HF-SCs）存在于一个特殊的生态位中，在那里它们作为一层极化的、静止的上皮细胞度过了很长时间。当足够的激活信号积累时，HF-SCs被动员起来促进组织再生和头发生长。在这里，我们发现转录因子LHX2对HF-SC生态位的结构组织在HF-SC行为中起着关键作用。通过对体内HF-SCs的全基因组染色质和转录谱分析，我们发现LHX2直接激活了协调细胞骨架动力学和粘附的基因。LHX2的条件消融导致细胞总体紊乱和生态位内HF-SC极化。LHX2的缺失导致HF-SC的静止和毛发锚定无法维持，以及小生境向皮脂腺的逐渐转变。这些研究结果表明，LHX2在毛囊结构和功能中的需求是基于生态位组织的。
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.