SOX9: a stem cell transcriptional regulator of secreted niche signaling factors.
SOX9: a stem cell transcriptional regulator of secreted niche signaling factors.
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DOI：
10.1101/gad.233247.113
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发表时间：
2014-02-15
影响因子：
10.5
通讯作者：
Fuchs E
中科院分区：
文献类型：
--
作者：
Kadaja M;Keyes BE;Lin M;Pasolli HA;Genander M;Polak L;Stokes N;Zheng D;Fuchs E
毛囊（HF）经历周期性的生长期，其由干细胞（SC）提供燃料。通过有条件地靶向成体HF-SC中的Sox9，Kadaja等人发现，Sox9对干性和HF向下生长至关重要。许多S0X9敏感性靶标编码细胞外因子，最显著的是激活素/pSMAD2信号传导的增强子。受损的激活素信号转导重现了SOX 9依赖性缺陷，激活素部分挽救了它们。这些发现揭示了SOX 9在调节成人HF-SC维持中的作用，以及SC在通过小生境内的非细胞自主信号传导协调其自身行为中的作用。毛囊（HF）经历周期性的生长期，其由静止毛囊基部的干细胞（SC）提供燃料。HF-SC的形成发生在HF发展过程中，需要转录因子SOX 9。SOX 9是否以及如何在HF-SC维护中发挥作用仍然未知。通过有条件地靶向成人HF-SC中的Sox 9，我们表明Sox 9对于维持它们至关重要。S0X9缺陷的HF-SC仍然从静止过渡到增殖并启动随后的毛发周期。然而，一旦被激活，凸起的HF-SC开始分化为表皮细胞，其天然缺乏SOX 9。此外，随着HF-SC数量的减少，外根鞘的产生不能持续，HF向下生长过早停止。为了探索这一机制，我们使用RNA测序（RNA-seq）来鉴定SOX9依赖的转录变化，并使用染色质免疫沉淀（ChIP）和深度测序（ChIP-seq）来鉴定HF-SC中的SOX9结合基因。有趣的是，一大群S0X9敏感性靶标编码细胞外因子，最显著的是激活素/pSMAD2信号传导的增强子。此外，损害激活素信号重现了SOX 9依赖性缺陷，激活素部分挽救了它们。总的来说，我们的研究结果揭示了SOX 9在调节成体HF-SC维持和抑制小生境中的表皮分化中的作用。此外，我们的研究揭示了SC在协调自己的行为中的作用，部分是通过生态位内的非细胞自主信号传导。
Hair follicles (HFs) undergo cyclical periods of growth, which are fueled by stem cells (SCs). By conditionally targeting Sox9 in adult HF-SCs, Kadaja et al. found that SOX9 is essential for stemness and HF downgrowth. Numerous SOX9-sensitive targets encode extracellular factors, most notably enhancers of Activin/pSMAD2 signaling. Compromising Activin signaling recapitulates SOX9-dependent defects, and Activin partially rescues them. These findings reveal roles for SOX9 in regulating adult HF-SC maintenance and a role for SCs in coordinating their own behavior through non-cell-autonomous signaling within the niche. Hair follicles (HFs) undergo cyclical periods of growth, which are fueled by stem cells (SCs) at the base of the resting follicle. HF-SC formation occurs during HF development and requires transcription factor SOX9. Whether and how SOX9 functions in HF-SC maintenance remain unknown. By conditionally targeting Sox9 in adult HF-SCs, we show that SOX9 is essential for maintaining them. SOX9-deficient HF-SCs still transition from quiescence to proliferation and launch the subsequent hair cycle. However, once activated, bulge HF-SCs begin to differentiate into epidermal cells, which naturally lack SOX9. In addition, as HF-SC numbers dwindle, outer root sheath production is not sustained, and HF downgrowth arrests prematurely. Probing the mechanism, we used RNA sequencing (RNA-seq) to identify SOX9-dependent transcriptional changes and chromatin immunoprecipitation (ChIP) and deep sequencing (ChIP-seq) to identify SOX9-bound genes in HF-SCs. Intriguingly, a large cohort of SOX9-sensitive targets encode extracellular factors, most notably enhancers of Activin/pSMAD2 signaling. Moreover, compromising Activin signaling recapitulates SOX9-dependent defects, and Activin partially rescues them. Overall, our findings reveal roles for SOX9 in regulating adult HF-SC maintenance and suppressing epidermal differentiation in the niche. In addition, our studies expose a role for SCs in coordinating their own behavior in part through non-cell-autonomous signaling within the niche.
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影响因子：
23.9
作者：
Folgueras AR;Guo X;Pasolli HA;Stokes N;Polak L;Zheng D;Fuchs E
通讯作者：
Fuchs E
影响因子：
11.4
作者：
Lefebvre, V;Li, P;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
10.5
作者：
Akiyama, H;Chaboissier, MC;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
5.3
作者：
Lefebvre, V;Huang, WD;deCrombrugghe, B
通讯作者：
deCrombrugghe, B
影响因子：
64.5
作者：
Hsu YC;Pasolli HA;Fuchs E
通讯作者：
Fuchs E