Role of locus-specific transposable element expression in development

Transposable elements (TEs) are mobile genetic elements that can affect gene expression through their own regulatory sequences. TE expression has been associated with various developmental disorders. Nevertheless, the role of TEs in development is not fully understood. Understanding the function of TEs in development requires studying locus-specific TE expression in single cells. However, due to the repetitive nature of TEs, this has been challenging. To address this challenge, I have developed a novel method called CELLO-seq, which uses long-read single-cell RNA sequencing to study locus-specific TE expression in individual cells. I propose to employ CELLO-seq and a wide range of functional tools to investigate the function of locus-specific TE expression in development and cell fate decision. I will test specific hypotheses about the role of locus-specific TE expression in mouse preimplantation and embryonic stem cells. First, I will evaluate TE expression heterogeneity between cells. Second, I will study deterministic TE expression within cells. Third I will test the function of TE expression in regulating genes important for cell fate decision. The results will provide novel insights into the role of TEs in development, revealing regulatory mechanisms that govern cell fate decision, with implications for stem cell, developmental, and regenerative biology.