The changing mouse embryo transcriptome at whole tissue and single-cell resolution.

Area of Science:

• Developmental Biology
• Genomics
• Transcriptomics

Background:

• Mammalian embryogenesis involves complex gene expression to establish tissue identity.
• Understanding developmental gene regulation is crucial for developmental biology.

Purpose of the Study:

• To systematically quantify the mouse polyA-RNA transcriptome during embryonic development.
• To characterize the global structure and key drivers of differential gene expression.
• To identify regulatory mechanisms, including transcription factor networks and epigenomic profiles.

Main Methods:

• Systematic quantification of mouse polyA-RNA from embryonic day 10.5 to birth across 17 tissues.
• Decomposition of tissue-level transcriptomes using single-cell RNA sequencing (scRNA-seq).
• Integration of promoter sequence motifs with ENCODE epigenomic profiles and IDEAS models.

Main Results:

• The developmental transcriptome is globally structured by cytodifferentiation, body-axis, and cell-proliferation gene sets.
• Neurogenesis and haematopoiesis significantly dominate differential gene expression and cell types.
• A promoter de-repression mechanism involving repressors was identified in neuronal expression clusters.
• scRNA-seq analysis of developing limb identified 25 cell types with inferred lineage relationships.

Conclusions:

• Dynamic gene expression, particularly neurogenesis and haematopoiesis, shapes mammalian embryonic development.
• Promoter de-repression is a key regulatory mechanism in neuronal development.
• Integrated analysis of transcriptomic and epigenomic data provides valuable resources for developmental research.