Single-cell analysis of isoform switching and transposable element expression during preimplantation embryonic development

PLoS Biol. 2024 Feb 16;22(2):e3002505. doi: 10.1371/journal.pbio.3002505. eCollection 2024 Feb.

Abstract

Alternative splicing is an essential regulatory mechanism for development and pathogenesis. Through alternative splicing one gene can encode multiple isoforms and be translated into proteins with different functions. Therefore, this diversity is an important dimension to understand the molecular mechanism governing embryo development. Isoform expression in preimplantation embryos has been extensively investigated, leading to the discovery of new isoforms. However, the dynamics of isoform switching of different types of transcripts throughout the development remains unexplored. Here, using single-cell direct isoform sequencing in over 100 single blastomeres from the mouse oocyte to blastocyst stage, we quantified isoform expression and found that 3-prime partial transcripts lacking stop codons are highly accumulated in oocytes and zygotes. These transcripts are not transcription by-products and might play a role in maternal to zygote transition (MZT) process. Long-read sequencing also enabled us to determine the expression of transposable elements (TEs) at specific loci. In this way, we identified 3,894 TE loci that exhibited dynamic changes along the preimplantation development, likely regulating the expression of adjacent genes. Our work provides novel insights into the transcriptional regulation of early embryo development.

MeSH terms

  • Animals
  • DNA Transposable Elements* / genetics
  • Embryonic Development* / genetics
  • Female
  • Mice
  • Pregnancy
  • Protein Isoforms / genetics
  • Single-Cell Analysis
  • Zygote

Substances

  • DNA Transposable Elements
  • Protein Isoforms

Grants and funding

This work was supported by grants from the National Key Research and Development Program of China (2020YFA0112201 to XF), the National Natural Science Foundation of China (32071451 to XF), the Guangdong Provincial Pearl River Talents Program (2021QN02Y747 to XF), and the R&D Program of Guangzhou National Laboratory (SRPG21-001 to XF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.