What question did this study set out to answer?

This research aims to investigate the molecular changes during the maternal-to-zygotic transition in human and pig embryos.

March 7, 2026Open Access

Integrated Single-Cell analysis Reveals molecular correlation of maternal-to-zygotic transition between human and pig embryo

Key Points

This research aims to investigate the molecular changes during the maternal-to-zygotic transition in human and pig embryos.
Integrated single-cell RNA sequencing data from 139 human and porcine samples
Utilized Seurat v5 for data integration with reciprocal principal component analysis
Conducted orthologous gene mapping, dimensionality reduction, and differential gene expression analysis
Performed functional enrichment analysis and pseudotime trajectory inference using Monocle3
Reconstructed transcription factor regulatory networks using SCENIC v1.3.1.
Identified both conserved and species-specific features during early embryonic development
Noted differences in core transcription factors associated with major zygotic genome activation events between species
Found chromatin remodeling-related genes highly enriched among maternal transcripts with functional conservation
MT genes showed higher average expression levels in human embryos than in pig embryos at all stages
Observed pronounced heterogeneity in ATP8 expression among pig embryos.

Abstract

Early embryonic development begins with a transcriptionally quiescent phase that is regulated by maternally deposited products. Developmental control subsequently shifts to the zygotic genome through zygotic genome activation (ZGA) during the maternal-to-zygotic transition. This transition represents a critical developmental window that governs embryonic timing and cell fate determination. Notably, the characteristics and temporal dynamics of ZGA occur in distinct waves and display substantial divergence across species. Single-cell RNA sequencing data from 139 human and porcine samples, spanning developmental stages from the oocyte to the morula, were integrated using Seurat v5 with reciprocal principal component analysis. Downstream analyses included orthologous gene mapping, dimensionality reduction, differential gene expression analysis, functional enrichment analysis, and pseudotime trajectory inference using Monocle3. Transcription factor (TF) regulatory networks were reconstructed using SCENIC (v1.3.1). Our analyses revealed both conserved and species-specific features during embryonic development from the oocyte to the morula stage in humans and pigs. The core TFs associated with major ZGA events differed markedly between the two species, indicating species-specific regulatory programs. In contrast, chromatin remodeling–related genes were highly enriched among maternal transcripts and exhibited functional conservation across species. Furthermore, MT genes showed consistently higher average expression levels in human embryos compared with porcine embryos across all examined stages, whereas ATP8 expression demonstrated pronounced heterogeneity among pig embryos. In conclusion, early embryonic development in humans and pigs is governed by conserved regulatory mechanisms underlying key biological processes, such as chromatin remodeling and major ZGA events. However, notable differences in metabolic activity and signaling pathways suggest the presence of species-specific adaptive strategies during early development.

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