在细胞与细胞融合过程中,TFEB控制人体合成的表达
Meagan N Esbin1, Liza Dahal2, Vinson B Fan2
1Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California 94720, USA; jmlim@berkeley.edu meagan_esbin@berkeley.edu.
转录因子TFEB在胎盘发育过程中对同胞细胞融合至关重要. TFEB直接调节Syncytin-1和Syncytin-2的表达,这对热囊细胞融合至关重要.
科学领域:
- 生殖生物学 生殖生物学
- 细胞生物学 细胞生物学
- 发育生物学是发展生物学.
背景情况:
- 胎盘是胎儿发育必不可少的临时器官,促进营养和气体交换.
- 胎盘中关键细胞类型的syncytiotrophoblasts通过由Syncytin-1和Syncytin-2介导的细胞细胞融合形成.
- 对Syncytin-1和Syncytin-2表达的上游调节者仍然在很大程度上没有特征.
研究的目的:
- 识别和描述控制人类热细胞细胞融合的转录调节剂.
- 为了研究转录因子TFEB在同聚氨基细胞分化和Syncytin表达中的作用.
主要方法:
- 在BeWo细胞中使用了CRISPR-Cas9基因编辑,这是一种用于合成细胞发育的体外模型.
- 对TFEB的核转位,染色体相互作用和与Syncytin促进剂的结合进行了分析.
- 评估TFEB对 lysosomal基因表达和生物发生的影响进行了.
主要成果:
- 转录因子TFEB是需要在syncytiotrophoblasts中进行细胞融合的.
- TFEB转移到核中,直接与Syncytin-1和Syncytin-2的促进体结合,调节它们的表达.
- 消去TFEB并没有显著影响溶解体基因表达或在分化细胞中的生物发生.
结论:
- TFEB在调节人体syncytin表达和促进 trofhoblast 融合方面发挥着至关重要的,以前未被承认的作用.
- 这一发现揭示了TFEB的新功能,超出了它在自和 lysosomal biogenesis 中已知的作用.
- TFEB代表了理解和调节胎盘发育的潜在目标.
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