Transcription Factor CTIP2 Maintains Hair Follicle Stem Cell Pool and Contributes to Altered Expression of LHX2 and NFATC1.
Transcription Factor CTIP2 Maintains Hair Follicle Stem Cell Pool and Contributes to Altered Expression of LHX2 and NFATC1.
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DOI：
10.1038/jid.2015.281
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Indra AK
中科院分区：
文献类型：
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作者：
Bhattacharya S;Wheeler H;Leid M;Ganguli-Indra G;Indra AK
转录因子CTIP 2（COUP-TF相互作用蛋白2），也称为BCL 11 B，在胚胎和成人皮肤的毛囊中表达。Ctip 2基因缺失小鼠在胚胎发育过程中表现出毛囊密度降低。相比之下，表皮中Ctip 2的条件性失活（Ctip 2 ep −/−小鼠）导致毛发周期第二阶段的休止期缩短，并过早进入生长期，而毛囊数量没有可检测到的变化。与野生型小鼠的相应细胞相比，Ctip 2 ep −/−小鼠隆突干细胞龛的角质形成细胞增殖更多，凋亡减少。然而，与保留静止卵泡干细胞的Ctip 2L 2/L2小鼠相比，缺乏CTIP 2的小鼠中卵泡干细胞的过早激活导致该干细胞区室的耗尽。CTIP 2调节毛囊形成期间编码EGFR和NOTCH 1的基因的表达，以及成人皮肤中正常毛发周期期间编码NFATC 1和LHX 2的基因的表达。在缺乏CTIP 2的小鼠中，大多数这些基因的表达被破坏，这些改变可能是Ctip 2-null和Ctip 2 ep −/−小鼠表型的基础。CTIP 2似乎是一个转录组织者，整合毛囊形态发生和毛发周期中多种信号线索的输入。
Transcription factor CTIP2 (COUP-TF-interacting protein 2), also known as BCL11B, is expressed in hair follicles of embryonic and adult skin. Ctip2-null mice exhibit reduced hair follicle density during embryonic development. In contrast, conditional inactivation of Ctip2 in epidermis (Ctip2ep−/− mice) leads to a shorter telogen and premature entry into anagen during the second phase of hair cycling without a detectable change in the number of hair follicles. Keratinocytes of the bulge stem cells niche of Ctip2ep−/− mice proliferate more and undergo reduced apoptosis than the corresponding cells of wild-type mice. However, premature activation of follicular stem cells in mice lacking CTIP2 leads to the exhaustion of this stem cell compartment in comparison to Ctip2L2/L2 mice, which retained quiescent follicle stem cells. CTIP2 modulates expression of genes encoding EGFR and NOTCH1 during formation of hair follicles, and those encoding NFATC1 and LHX2 during normal hair cycling in adult skin. The expression of most of these genes is disrupted in mice lacking CTIP2 and these alterations may underlie the phenotype of Ctip2-null and Ctip2ep−/− mice. CTIP2 appears to serve as a transcriptional organizer that integrates input from multiple signaling cues during hair follicle morphogenesis and hair cycling.