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试验室方法揭示了内分泌干扰物诱导的表皮突变发生的潜在分子机制
Jake D Lehle1, Yu-Huey Lin1, Amanda Gomez1
1Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, United States.
eLife
|October 3, 2024
概括
干扰内分泌的化学物质,如双S (BPS) 引起表观遗传变化. 这些变化在几代人中持续存在,BPS在随后的细胞代中诱导了新的表皮.
科学领域:
- 内分泌学 在内分泌学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 毒理学 毒理学 毒理学
背景情况:
- 内分泌干扰化学物质 (EDC) 干扰激素信号传递,因为它们与内源性激素的结构相似.
- EDCs可以引起表观遗传变化 (表观突变) 和差异基因表达 (DEGs),可能导致疾病.
- 由于EDC诱导的多代性长期存在,导致人们对其传播机制提出了疑问.
研究的目的:
- 为了研究双S (BPS) 对表观遗传编程的细胞类型特异性影响.
- 探索EDC诱导的表皮突变引入和传播的基础分子机制.
- 确定EDC暴露是否导致细胞类型特定的敏感性和与激素受体表达相关.
主要方法:
- 培养的多能细胞 (iPS),体细胞 (Sertoli,颗粒细胞) 和原始生殖细胞类细胞 (PGCLC) 暴露于BPS.
- 在不同细胞类型中分析BPS诱导的表皮和DEG.
- 在暴露于BPS的iPS细胞中诱导PGCLCs的分化,以评估表皮转化保留和新奇性.
主要成果:
- 在细胞类型中观察到BPS诱导的表皮和DEG的不同发病率.
- 在体细胞和多能细胞中的激素反应元素附近,与差异激素受体表达相关的表皮和DEGs,但不是生殖细胞.
- 暴露于BPS的iPS细胞分化为PGCLCs保留了表皮和DEG,但超过90%的特定表皮/DEG被新型细胞取代.
结论:
- 存在细胞类型特异性对BPS诱导的表皮移动的敏感性,与激素受体表达有关.
- 建议一种独特的机制,用于EDC诱导的表皮化状态的跨代传播.
- 需要进行进一步的研究,以阐明EDC表皮转化遗传的精确分子路径.
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