Gene Regulatory Mechanisms Driving Totipotency Induction in Human Stem Cells

About This Grant

ABSTRACT Infertility remains a global public health challenge, with early developmental failure accounting for a significant proportion of unsuccessful pregnancies. Among the critical processes governing early developmental competence, RNA splicing plays a central role by coordinating transcriptional output, shaping chromatin architecture, and influencing protein synthesis. Yet the mechanisms by which splicing governs these multilayered regulatory systems during the earliest stages of development remain poorly defined. This research investigates the multilayered consequences of splicing dysfunction in an in vitro model of early human development, focusing on how disruptions in RNA processing alter structural genome organization and the regulation of gene expression. Through integrative transcriptomic, epigenomic, and proteomic profiling of cells in vitro, I aim to define how splicing inhibition alters polymerase activity, chromatin architecture, and gene translation. A key objective is to identify the cascade of molecular events—across nuclear and cytoplasmic compartments—that links shifts in RNA splicing efficiency to cell potential. By examining these mechanisms, this project will reveal how splicing regulation safeguards developmental trajectories. Ultimately, this work will advance fundamental knowledge of gene regulation in early development and illuminate molecular mechanisms underlying infertility. These findings hold long-term promise for improving diagnostic strategies and public health interventions aimed at reducing the burden of reproductive failure.