Temporal-Spatial Establishment of Initial Niche for the Primary Spermatogonial Stem Cell Formation Is Determined by an ARID4B Regulatory Network.
Temporal-Spatial Establishment of Initial Niche for the Primary Spermatogonial Stem Cell Formation Is Determined by an ARID4B Regulatory Network.
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DOI：
10.1002/stem.2597
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Wu MY
中科院分区：
文献类型：
--
作者：
Wu RC;Zeng Y;Chen YF;Lanz RB;Wu MY
在新生儿睾丸发育过程中，位于中心的性腺细胞迁移到精索基底膜，在那里，与支持细胞建立的生态位的物理接触对于性腺细胞向精原干细胞（SSCs）的转变是必不可少的。为了在有限的阶段中为特定位置的淋细胞向ssc的转变提供结构支持和信号刺激，生态位的时空建立至关重要。迄今为止，引导支持细胞建立初始干细胞生态位的因素在很大程度上仍然未知。利用支持细胞特异性Arid4b敲除（Arid4bSCKO）小鼠，我们证明了在淋细胞向SSC过渡阶段，消融富含at的相互作用结构域4B （Arid4b）导致支持细胞从精索基底膜异常脱离，这表明无法为SSC的形成建立一个生态位。在没有生态位环境支持的情况下，Arid4bSCKO患者睾丸中的性腺细胞表现出细胞分布紊乱并发生凋亡。性腺细胞分化为精原细胞谱系的承诺被破坏，ssc自我更新和分化的能力也受到损害。基因表达谱揭示了Arid4bSCKO睾丸表型变化的分子机制，通过鉴定作为ARID4B下游效应因子的干细胞生态位功能的重要基因，包括编码间隙连接蛋白α -1、KIT配体、抗mllerian激素、胶质细胞系源性神经营养因子、抑制素α、抑制素β和细胞色素P450家族26亚家族b多肽1的基因。我们的研究结果确定ARID4B是一个信号网络的主调节器，该信号网络在关键的淋细胞向ssc过渡阶段控制生态位的建立，从而控制淋细胞和ssc的命运。
During neonatal testis development, centrally located gonocytes migrate to basement membrane of the seminiferous cords, where physical contact with a niche established by Sertoli cells is essential for transition of gonocytes into spermatogonial stem cells (SSCs). To provide structural support and signaling stimuli for the gonocyte-to-SSC transition that occurs at a specific location during a finite phase, temporal-spatial establishment of the niche is critical. To date, the factors that guide Sertoli cells to establish the initial stem cell niche remain largely unknown. Using the Sertoli cell-specific Arid4b knockout (Arid4bSCKO) mice, we demonstrated that ablation of AT-rich interaction domain 4B (ARID4B) resulted in abnormal detachment of Sertoli cells from the basement membrane of seminiferous cords during the gonocyte-to-SSC transition phase, suggesting failure to establish a niche for the SSC formation. Without support by a niche environment, gonocytes showed disarranged cell distribution in the Arid4bSCKO testes and underwent apoptosis. The commitment of gonocytes to differentiate into the spermatogonial lineage was broken and the capability of SSCs to self-renew and differentiate was also impaired. Gene expression profiling revealed the molecular mechanisms responsible for the phenotypic changes in the Arid4bSCKO testes, by identifying genes important for stem cell niche function as downstream effectors of ARID4B, including genes that encode gap junction protein alpha-1, KIT ligand, anti-Müllerian hormone, Glial cell-line derived neurotrophic factor, inhibin alpha, inhibin beta, and cytochrome P450 family 26 subfamily b polypeptide 1. Our results identified ARID4B as a master regulator of a signaling network that governs the establishment of a niche during the critical gonocyte-to-SSC transition phase to control the fate of gonocytes and SSCs.
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DOI：
10.1002/bdrc.20041
发表时间：
2005-06-01
期刊：
Birth defects research. Part C, Embryo today : reviews
影响因子：
--
作者：
Tres, Laura L;Kierszenbaum, Abraham L
通讯作者：
Kierszenbaum, Abraham L
影响因子：
13.8
作者：
Lu, Rui;Wang, Gang Greg
通讯作者：
Wang, Gang Greg
影响因子：
3.7
作者：
Dovere L;Fera S;Grasso M;Lamberti D;Gargioli C;Muciaccia B;Lustri AM;Stefanini M;Vicini E
通讯作者：
Vicini E
影响因子：
2.7
作者：
Garcia, Thomas Xavier;DeFalco, Tony;Capel, Blanche;Hofmann, Marie-Claude
通讯作者：
Hofmann, Marie-Claude
影响因子：
2.7
作者：
MARZIALI, G;LAZZARO, D;SORRENTINO, V
通讯作者：
SORRENTINO, V