Single-Cell Analysis of Alternative Splicing and Gene Regulatory Network Reveals Remarkable Expression and Regulation...

Area of Science:

• Developmental Biology
• Genomics
• Molecular Biology

Background:

• Single-cell RNA sequencing (scRNA-seq) advanced understanding of gene expression variability.
• Few scRNA-seq studies have detailed isoform and exon-level expression dynamics in early human embryos.
• Systematic investigation of gene expression dynamics during human early embryonic development is lacking.

Purpose of the Study:

• To systematically explore gene expression dynamics in human early embryonic development.
• To integrate gene expression levels with alternative splicing, isoform switching, and regulatory networks.
• To provide insights into gene dynamic characteristics for developmental biology and disease research.

Main Methods:

• Utilized single-cell RNA sequencing (scRNA-seq) data from human early embryos (E3-E7).
• Integrated analysis of gene expression levels, alternative splicing, and isoform switching.
• Explored gene regulatory networks and transcription factor binding motifs (TFBMs).

Main Results:

• Genes with significant changes in expression, splicing, and isoform usage decreased from E3 to E7.
• These variations are complementary and differ significantly across developmental stages and sexes.
• More genes showed alternative splicing and isoform switching variations than expression level changes between sexes at E3.
• Identified stage-specific gene regulatory modules and dynamic TFBM usage.

Conclusions:

• This study provides comprehensive insights into gene dynamic characteristics during human early embryonic development.
• Integrative analysis of expression, splicing, and regulatory networks deepens understanding of developmental processes.
• Findings contribute to basic developmental biology and have implications for regenerative medicine and developmental diseases.