A team of brilliant researchers, in collaboration with our university scientists, led by Tomofuji et al., has made groundbreaking discoveries about the X chromosome and its unique behavior in genetic regulation. This innovative study, recently published in Cell Genomics, reveals how certain genes on the X chromosome can “escape” from a process known as X chromosome inactivation (XCI). This process typically silences one of the X chromosomes in females, but some genes manage to remain active—a phenomenon that varies across different cell types and tissues.

The researchers developed a cutting-edge tool called scLinaX to measure these escaping genes using advanced single-cell RNA sequencing techniques. Their findings are astonishing—lymphocytes, a type of white blood cell, exhibit a stronger gene escape than myeloid cells. This discovery was further validated through multiome datasets (scLinaX-multi), revealing that gene escape is consistent at both gene activity and chromatin levels.

Additionally, the team extended their analysis to human multiple-organ single-cell RNA sequencing datasets and found that immune-related tissues and lymphocytes often show a high degree of gene escape. This research also explored how these escape patterns might influence the relationship between genetic variations and traits or diseases across different sexes.

This pioneering study not only highlights the diverse patterns of gene escape from XCI across various cell types and tissues but also provides new insights into genetic regulation with significant implications for health and disease.

Ponpan Matangkasombut

Co-author as part of Asian Immune Diversity Atlas (AIDA) Network