德国亥姆霍兹慕尼黑中心Maria-Elena Torres-Padilla研究团队发现,转录起始图谱揭示早期哺乳动物发育中基因和转座子表达的调控原则。相关论文于2025年1月20日在线发表在《细胞》杂志上。
研究人员开发了Smart-seq+5′,一种具有高灵敏度、全长转录覆盖并能够同时捕捉单细胞和单胚胎5′转录信息的方法。通过使用Smart-seq+5′,研究人员对5种哺乳动物物种的34个发育阶段进行了分析,广泛表征了早期发育中在胚胎基因组转录激活(EGA)前、期间和之后的转录谱。
研究人员展示了跨物种广泛的转座子(TE)驱动的转录现象,特别是DNA转座子。研究人员鉴定出19657个TE驱动的基因转录本,表明在演化时间尺度上,转座子在早期发育中被广泛共用。转座子在各物种中显示出相似的表达动态以及物种特异性的表达模式,提示其调控具有共享性和分化性。
该研究为理解哺乳动物发育中的转录调控提供了一个强大的资源。
据介绍,EGA是一个重要的发育标志,标志着胚胎从母体控制中独立出来。在此过程中,哺乳动物中转录重编程的规模和调控机制仍然不甚清楚。
附:英文原文
Title: An atlas of transcription initiation reveals regulatory principles of gene and transposable element expression in early mammalian development
Author: Marlies E. Oomen, Diego Rodriguez-Terrones, Mayuko Kurome, Valeri Zakhartchenko, Lorenza Mottes, Kilian Simmet, Camille Noll, Tsunetoshi Nakatani, Carlos Michel Mourra-Diaz, Irene Aksoy, Pierre Savatier, Jonathan Gke, Eckhard Wolf, Henrik Kaessmann, Maria-Elena Torres-Padilla
Issue&Volume: 2025-01-20
Abstract: Transcriptional activation of the embryonic genome (EGA) is a major developmental landmark enabling the embryo to become independent from maternal control. The magnitude and control of transcriptional reprogramming during this event across mammals remains poorly understood. Here, we developed Smart-seq+5′ for high sensitivity, full-length transcript coverage and simultaneous capture of 5′ transcript information from single cells and single embryos. Using Smart-seq+5′, we profiled 34 developmental stages in 5 mammalian species and provide an extensive characterization of the transcriptional repertoire of early development before, during, and after EGA. We demonstrate widespread transposable element (TE)-driven transcription across species, including, remarkably, of DNA transposons. We identify 19,657 TE-driven genic transcripts, suggesting extensive TE co-option in early development over evolutionary timescales. TEs display similar expression dynamics across species and species-specific patterns, suggesting shared and divergent regulation. Our work provides a powerful resource for understanding transcriptional regulation of mammalian development.
DOI: 10.1016/j.cell.2024.12.013
Source: https://www.cell.com/cell/abstract/S0092-8674(24)01426-0