DNA hypomethylation activation Wnt/TCF7L2/TDRD1 pathway promotes spermatogonial stem cell formation

Wnt信号通路 DNA甲基化 生物 发起人 细胞生物学 转基因 基因 干细胞 分子生物学 信号转导 基因表达 遗传学
作者
Xiaomin Gao,Xiang Shi,Shujian Zhou,Chen Chen,Cai Hu,Qian Xia,Xinlin Li,Wen Gao,Ying Ding,Qisheng Zuo,Yani Zhang,Bichun Li
出处
期刊:Journal of Cellular Physiology [Wiley]
卷期号:237 (9): 3640-3650 被引量:3
标识
DOI:10.1002/jcp.30822
摘要

Abstract Detailed analysis of the regulatory mechanism of spermatogonia stem cell (SSCs) genesis can provide a novel strategy for the application of SSCs in the fields of transgenic animal production and regenerative medicine. Previous studies in this study showed that WNT signaling can positively regulate the formation of SSCs, but the exact regulatory mechanism is not clear. Here, we predicted the target gene of the Wnt/TCF7L2 pathway, namely TDRD1, by bioinformatics analysis. Functional studies revealed that overexpression of TDRD1 during RA‐induced SSCs formation in vitro significantly upregulated the expression of reproductive marker genes (Integrinβ1 and Integrinα6), and further flow cytometric analysis also confirmed that the formation efficiency of SSCs was significantly increased after overexpression of TDRD1; while interference with TDRD1 showed the exact opposite result. The in vivo experiments were consistent with the results of the in vitro experiments. Interestingly, although Wnt/TCF7L2 can promote the formation of SSCs, its function must be dependent on the expression of TDRD1, which was also repeatedly demonstrated as a target gene of the Wnt/TCF7L2 signaling pathway. Mechanistically, we found a large number of CpG sites in the TDRD1 promoter, and BSP analysis also confirmed that DNA methylation modifications in the TDRD1 promoter were significantly higher in embryonic stem cells than in SSCs, and further dual‐luciferase reporter system assays revealed that low DNA methylation modification levels could enhance TDRD1 promoter activity; although previous studies demonstrated that TCF7L2 could enrich in the TDRD1 promoter region, the binding of the two was dependent on low DNA methylation modification. Taken together, we confirmed that low DNA methylation mediates Wnt/TCF7L2 regulation of TDRD1 to promote the formation of SSCs, providing a basis for SSCs in improving animal productivity.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
舒心白山完成签到 ,获得积分20
刚刚
浅尝离白应助zhw采纳,获得30
刚刚
刚刚
研友_VZG7GZ应助有点怪采纳,获得10
刚刚
木木发布了新的文献求助10
1秒前
2秒前
大个应助卓延恶采纳,获得10
3秒前
lucky完成签到,获得积分10
3秒前
cyw9608发布了新的文献求助20
4秒前
香蕉觅云应助Kaysarr采纳,获得10
6秒前
youuuu发布了新的文献求助10
7秒前
7秒前
叶子发布了新的文献求助10
8秒前
9秒前
Khr1stINK完成签到,获得积分10
10秒前
SciGPT应助可爱怀莲采纳,获得10
10秒前
11秒前
木木完成签到,获得积分10
11秒前
科研通AI2S应助fifteen采纳,获得10
12秒前
卡卡西西西完成签到,获得积分10
14秒前
nianxunxi完成签到,获得积分10
14秒前
15秒前
15秒前
神勇的长颈鹿完成签到 ,获得积分10
15秒前
坚强怀绿发布了新的文献求助10
16秒前
16秒前
干净香寒发布了新的文献求助20
17秒前
17秒前
18秒前
cln完成签到,获得积分10
19秒前
西瓜西瓜关注了科研通微信公众号
19秒前
tutu发布了新的文献求助10
20秒前
斯文败类应助Ustinian采纳,获得30
20秒前
柚子发布了新的文献求助10
20秒前
sss312完成签到,获得积分10
21秒前
21秒前
火山发布了新的文献求助10
22秒前
田様应助上官聪展采纳,获得10
23秒前
wjy发布了新的文献求助10
23秒前
Lovuan发布了新的文献求助10
23秒前
高分求助中
Evolution 10000
юрские динозавры восточного забайкалья 800
English Wealden Fossils 700
Distribution Dependent Stochastic Differential Equations 500
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
A new species of Velataspis (Hemiptera Coccoidea Diaspididae) from tea in Assam 500
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3157832
求助须知:如何正确求助?哪些是违规求助? 2809154
关于积分的说明 7880665
捐赠科研通 2467655
什么是DOI,文献DOI怎么找? 1313641
科研通“疑难数据库(出版商)”最低求助积分说明 630467
版权声明 601943