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Peer-reviewedCC BY-NC-NDNature communications

Single-cell TimeLapse-seq reveals MTA is an essential retrotransposon orchestrating mouse zygotic genome activation.

  • You Wu1,2,3
  • Hanxi Shi1
  • Rushuang Yan2,3,4
  • Jiang Wu1
  • Lei Yang2,3
  • Lingfeng Xu1
  • Xiaochen Kou1,3
  • Yanhong Zhao1,3
  • Xuelian Liu2,3,4
  • Lingling Lai1
  • Silin Tian1
  • Yujie Hu1
5 more authors
  • Qiyue Wang1
  • Hong Wang1,3
  • Shaorong Gao5,6,7,8
  • Xiao-Ou Zhang9,10
  • Yawei Gao11,12,13
13 affiliations
  1. 1Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translation Research Center, Shanghai First Maternity & Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
  2. 2Department of Reproductive Medicine Center, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
  3. 3Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China.
  4. 4Sycamore Research Institute of Life Sciences, Shanghai, China.
  5. 5Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translation Research Center, Shanghai First Maternity & Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China. [email protected].
  6. 6Department of Reproductive Medicine Center, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China. [email protected].
  7. 7Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China. [email protected].
  8. 8Sycamore Research Institute of Life Sciences, Shanghai, China. [email protected].
  9. 9Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translation Research Center, Shanghai First Maternity & Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China. [email protected].
  10. 10Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China. [email protected].
  11. 11Department of Reproductive Medicine Center, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China. [email protected].
  12. 12Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, China. [email protected].
  13. 13Sycamore Research Institute of Life Sciences, Shanghai, China. [email protected].
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Abstract

Transposable elements (TEs) are temporally activated during mammalian early embryogenesis and are closely linked to zygotic genome activation (ZGA), yet their nascent transcriptional dynamics remain incompletely resolved owing to limited sensitivity and maternal RNA background. Here, we develop single-cell TimeLapse sequencing (scTL-seq), enabling allele-resolved detection of nascent RNA in individual embryos. Applying scTL-seq to mouse ZGA, we generate a refined transcriptional atlas of genes and TEs and identify the pronuclear (PN) stage activated genes and TEs. We found that transcription at PN stage is largely contributed by the maternal genome and enriched for genes highly transcribed in germinal vesicle oocytes. Similarly, Mouse Transcripts type-A (MTA) elements are transcribed in oocytes and highly active in PN stage. MTA knockdown disrupts zygotic gene activation and dysregulates hundreds of TE subfamilies, resulting in 1-cell embryo arrest. Using nascent transcripts, we further identify 662 TE-driven chimeric transcripts and show that TEs are essential for regulating key developmental genes, including Nfya, Setd2 and Tead4. Finally, we identify maternal transcription factors, including NOBOX, as potential regulators of MTA activation. Together, our study provides a high-resolution nascent transcriptome landscape of mouse ZGA and reveals vital regulatory roles of MTA retrotransposon in orchestrating early embryonic development.

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Cite

BibTeXRIS
BibTeX
@article{wu2026singlecell,
  title = {{Single-cell TimeLapse-seq reveals MTA is an essential retrotransposon orchestrating mouse zygotic genome activation.}},
  author = {You Wu and Hanxi Shi and Rushuang Yan and Jiang Wu and Lei Yang and Lingfeng Xu and Xiaochen Kou and Yanhong Zhao and Xuelian Liu and Lingling Lai and Silin Tian and Yujie Hu and Qiyue Wang and Hong Wang and Shaorong Gao and Xiao-Ou Zhang and Yawei Gao},
  journal = {Nature communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77750-3},
  url = {https://europepmc.org/article/MED/42907457},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Single-cell TimeLapse-seq reveals MTA is an essential retrotransposon orchestrating mouse zygotic genome activation.
AU  - You Wu
AU  - Hanxi Shi
AU  - Rushuang Yan
AU  - Jiang Wu
AU  - Lei Yang
AU  - Lingfeng Xu
AU  - Xiaochen Kou
AU  - Yanhong Zhao
AU  - Xuelian Liu
AU  - Lingling Lai
AU  - Silin Tian
AU  - Yujie Hu
AU  - Qiyue Wang
AU  - Hong Wang
AU  - Shaorong Gao
AU  - Xiao-Ou Zhang
AU  - Yawei Gao
PY  - 2026
DA  - 2026/09/22
JO  - Nature communications
DO  - 10.1038/s41467-026-77750-3
UR  - https://europepmc.org/article/MED/42907457
AB  - Transposable elements (TEs) are temporally activated during mammalian early embryogenesis and are closely linked to zygotic genome activation (ZGA), yet their nascent transcriptional dynamics remain incompletely resolved owing to limited sensitivity and maternal RNA background. Here, we develop single-cell TimeLapse sequencing (scTL-seq), enabling allele-resolved detection of nascent RNA in individual embryos. Applying scTL-seq to mouse ZGA, we generate a refined transcriptional atlas of genes and TEs and identify the pronuclear (PN) stage activated genes and TEs. We found that transcription at PN stage is largely contributed by the maternal genome and enriched for genes highly transcribed in germinal vesicle oocytes. Similarly, Mouse Transcripts type-A (MTA) elements are transcribed in oocytes and highly active in PN stage. MTA knockdown disrupts zygotic gene activation and dysregulates hundreds of TE subfamilies, resulting in 1-cell embryo arrest. Using nascent transcripts, we further identify 662 TE-driven chimeric transcripts and show that TEs are essential for regulating key developmental genes, including Nfya, Setd2 and Tead4. Finally, we identify maternal transcription factors, including NOBOX, as potential regulators of MTA activation. Together, our study provides a high-resolution nascent transcriptome landscape of mouse ZGA and reveals vital regulatory roles of MTA retrotransposon in orchestrating early embryonic development.
SN  - 2041-1723
ER  -