Comparative single-cell transcriptomic profiles of human androgenotes and parthenogenotes during early development

Area of Science:

• Reproductive Biology
• Developmental Biology
• Genomics

Background:

• Human androgenotes (AGs) and parthenogenotes (PGs) are models for studying early embryonic development.
• Understanding their transcriptomic differences is crucial for comprehending developmental potential.

Purpose of the Study:

• To analyze differential gene expression in AGs and PGs during early cell cycles.
• To determine the timing of embryonic genome activation (EGA) in both AGs and PGs.
• To characterize the single-cell transcriptional landscape of uniparental human embryos.

Main Methods:

• Generation of AGs via intracytoplasmic sperm injection and PGs via artificial oocyte activation.
• Single-cell RNA sequencing of AGs and PGs at various early developmental stages.
• Differential gene expression analysis and comparison of transcriptomic profiles.

Main Results:

• Significant differences in gene expression were observed between AGs and PGs, with an increasing number of differentially expressed genes (DEGs) from the first to the fourth cell cycle.
• AGs and PGs showed reduced EGA profiles in the first three cell cycles, with a notable spike in PGs by the fourth cell cycle.
• Maternal transcripts were prominent in later stages (third and fourth cell cycles) of PGs, associated with morphogenic progression.

Conclusions:

• AGs and PGs display complementary transcriptomic behaviors up to the fourth cell cycle.
• AGs exhibit paternal transcript contributions influencing cell cycle coordination and transcription regulation early on.
• PGs show a gradual EGA, with significant epigenetic reprogramming (methylation) by the fourth cell stage, challenging the notion of early cleavage stages as the sole totipotent entities.