Active Genetics & Molecular Biology Cells, Biochemistry & Physiology

Role of locus-specific transposable element expression in development

Funder Wellcome Charity-funded
Recipient organisation University of Oxford
Funding £3.1M
Period Aug 2024 — Jul 2032

In plain English

AI plain-English summary

A new method called CELLO-seq reads the full length of individual RNA molecules in single cells, allowing researchers to pinpoint exactly which copies of repetitive DNA sequences are active during early development. These repetitive sequences—known as transposable elements—make up nearly half the human genome but have been difficult to study because their identical copies are scattered across chromosomes, making it impossible to tell which specific copy is being expressed. This has left a major gap in understanding how they influence cell behaviour during development. The researcher will use CELLO-seq to track which transposable element copies are switched on in mouse embryos and embryonic stem cells, then test whether those elements help control genes that determine a cell's fate. This is fundamental science. The work aims to reveal basic regulatory mechanisms that govern how cells decide what to become—a process central to developmental biology. If successful, it could eventually inform stem cell therapies or regenerative medicine by showing how to manipulate cell identity. But the immediate value is in understanding a poorly understood layer of gene regulation that has been invisible until now.

View original technical description
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.

View the original record at the funder ↗

Researchers

Rebecca Berrens (EPMC Awardee)

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Transposable element-gene chimeric transcripts in neural tissues: functional impacts on gene expression and behaviour and their regulatory control across model systems

Original classification

Career Development Award

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