Loss of Raptor induces Sertoli cells into an undifferentiated state in mice.
Loss of Raptor induces Sertoli cells into an undifferentiated state in mice.
复制标题
DOI：
10.1093/biolre/ioac104
复制
发表时间：
2022-10-11
影响因子：
3.6
通讯作者：
Chen, Zhenguo
中科院分区：
文献类型：
--
作者：
Xie, Minyu;Hu, Xiao;Li, Lei;Xiong, Zhi;Zhang, Hanbin;Zhuang, Yuge;Huang, Zicong;Liu, Jinsheng;Lian, Jingyao;Huang, Chuyu;Xie, Qiang;Kang, Xiangjin;Fan, Yong;Bai, Xiaochun;Chen, Zhenguo
在哺乳动物中，睾丸发育是由性别决定Y染色体基因SRY的表达触发的，以在胎儿的性腺性别决定中提交支持细胞（SC）命运。已经鉴定了在SRY激活后促进睾丸途径所需的几种基因（即，SRY盒9（SOX 9））在胚胎中;然而，它在很大程度上仍然是未知的基因和机制参与稳定睾丸途径出生后和整个成年期。在此，我们报告出生后的男性与SC特异性缺失的猛禽表现出SC的独特身份和不利收购颗粒细胞样特征的情况下，沿着与管状结构和分散分布的SC和生殖细胞的损失。随后通过RNA测序进行的全基因组分析揭示了睾丸基因转录物的显著减少（即，Sox 9、Sox 8和抗苗勒管激素（Amh）），相反，卵巢基因（即，LIM/同源框基因9（Lhx 9）、叉头框L2（Foxl 2）和卵泡抑素（Fst））;这些变化通过免疫荧光和定量逆转录聚合酶链反应进一步证实。重要的是，共免疫荧光表明，猛禽缺陷诱导SC去分化成祖细胞状态;猛禽突变性腺表现出一些卵巢体细胞的功能，伴随着增强的雌性类固醇生成和升高的雌激素水平，但透明质酸3（ZP 3）阳性终末雌性化卵母细胞没有观察到。原代干细胞的体外实验表明，Raptor可能参与成纤维细胞生长因子9（FGF 9）诱导的干细胞间细胞连接的形成。我们的研究结果表明，Raptor是维持SC身份，稳定雄性途径，促进睾丸发育所必需的。 Raptor缺失诱导支持细胞进入未分化状态，并显示出一些卵巢体细胞特征。
In mammals, testis development is triggered by the expression of the sex-determining Y-chromosome gene SRY to commit the Sertoli cell (SC) fate at gonadal sex determination in the fetus. Several genes have been identified to be required to promote the testis pathway following SRY activation (i.e., SRY box 9 (SOX9)) in an embryo; however, it largely remains unknown about the genes and the mechanisms involved in stabilizing the testis pathway after birth and throughout adulthood. Herein, we report postnatal males with SC-specific deletion of Raptor demonstrated the absence of SC unique identity and adversely acquired granulosa cell-like characteristics, along with loss of tubular architecture and scattered distribution of SCs and germ cells. Subsequent genome-wide analysis by RNA sequencing revealed a profound decrease in the transcripts of testis genes (i.e., Sox9, Sox8, and anti-Mullerian hormone (Amh)) and, conversely, an increase in ovary genes (i.e., LIM/Homeobox gene 9 (Lhx9), Forkhead box L2 (Foxl2) and Follistatin (Fst)); these changes were further confirmed by immunofluorescence and quantitative reverse-transcription polymerase chain reaction. Importantly, co-immunofluorescence demonstrated that Raptor deficiency induced SCs dedifferentiation into a progenitor state; the Raptor-mutant gonads showed some ovarian somatic cell features, accompanied by enhanced female steroidogenesis and elevated estrogen levels, yet the zona pellucida 3 (ZP3)-positive terminally feminized oocytes were not observed. In vitro experiments with primary SCs suggested that Raptor is likely involved in the fibroblast growth factor 9 (FGF9)-induced formation of cell junctions among SCs. Our results established that Raptor is required to maintain SC identity, stabilize the male pathway, and promote testis development. Raptor deletion induced Sertoli cells into an undifferentiated state and showed some ovarian somatic cell features.
登录
查看更多内容
MTOR 卵母细胞阶段特异性影响决定小鼠颗粒细胞命运和卵母细胞质量
DOI：
10.1073/pnas.1800352115
发表时间：
2018-06-05
影响因子：
11.1
作者：
Guo J;Zhang T;Guo Y;Sun T;Li H;Zhang X;Yin H;Cao G;Yin Y;Wang H;Shi L;Guo X;Sha J;Eppig JJ;Su YQ
通讯作者：
Su YQ
影响因子：
3.5
作者：
Chassot, Anne-Amandine;Ranc, Fariba;Chaboissier, Marie-Christine
通讯作者：
Chaboissier, Marie-Christine
DOI：
10.1073/pnas.0600994103
发表时间：
2006-08-08
影响因子：
11.1
作者：
Gao, Fei;Maiti, Sourindra;Huff, Vicki
通讯作者：
Huff, Vicki
影响因子：
11.4
作者：
Malki, S;Nef, S;Boizet-Bonhoure, B
通讯作者：
Boizet-Bonhoure, B
影响因子：
4.6
作者：
Chaboissier, MC;Kobayashi, A;Schedl, A
通讯作者：
Schedl, A