Locus-specific expression of transposable elements in single cells with CELLO-seq.

Area of Science:

• Genomics
• Molecular Biology
• Developmental Biology

Background:

• Transposable elements (TEs) are crucial regulators of biological processes, including development and cancer.
• Measuring young TE expression is challenging for short-read sequencing due to repetitive sequences.
• Accurate quantification of TE expression is vital for understanding their functional roles.

Purpose of the Study:

• To develop and apply a novel method for precise measurement of transposable element (TE) expression at unique loci in single cells.
• To investigate the locus-specific expression patterns of both young and old TEs in mouse and human cells.
• To explore the regulatory relationships between individual TEs and their putative regulators.

Main Methods:

• Single CELl LOng-read RNA-sequencing (CELLO-seq) was employed, combining long-read sequencing with computational analysis.
• CELLO-seq was utilized to profile TE expression in two-cell mouse blastomeres and human induced pluripotent stem cells.
• Simulations were performed to assess the mapping confidence of short reads from young TEs.

Main Results:

• CELLO-seq successfully enabled the measurement of TE expression at unique loci across species.
• Both young and old TEs demonstrated locus-specific expression patterns in mouse and human cells.
• Analysis revealed significant heterogeneity in TE expression correlations with regulators, suggesting diverse regulatory mechanisms.

Conclusions:

• CELLO-seq is a powerful tool for accurately quantifying transposable element expression in single cells.
• TEs exhibit locus-specific regulation and functional heterogeneity, impacting genome dynamics.
• This study provides new insights into the complex regulatory networks governing transposable elements in mammals.