Aging activates escape of the silent X chromosome in the female mouse hippocampus

Science Advances, Год журнала: 2025, Номер 11(10)

Опубликована: Март 5, 2025

Women live longer than men and exhibit less cognitive aging. The X chromosome contributes to sex differences, as females harbor an inactive (Xi) active (Xa), in contrast males with only Xa. Thus, reactivation of silent Xi genes may contribute differences. We use allele-specific, single-nucleus RNA sequencing show that aging remodels transcription the Xa across hippocampal cell types. Aging preferentially changed gene expression on X's relative autosomes. Select underwent activation, new escape cells including dentate gyrus, critical learning memory. Expression escapee Plp1, a myelin component, was increased hippocampus female mice parahippocampus women. AAV-mediated Plp1 elevation gyrus male improved cognition. Understanding how confer advantage could lead novel targets counter brain disease both sexes.

Язык: Английский

---

Asian diversity in human immune cells

Cell, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

---

Escape from X-chromosome inactivation at KDM5C is driven by promoter-proximal DNA elements and enhanced by domain context

Human Molecular Genetics, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

Abstract Over 20% of human X-linked genes escape from X-chromosome inactivation (XCI), and are important contributors to sex differences in gene expression. Candidate factors involved have been identified through enrichment analyses include both regional as well promoter-proximal elements; however, functional testing is limited. Using vivo vitro mouse models, we refine a region just 2.6 kb the KDM5C able drive XCI. Transgenes Kdm5c XCI; one three more than 200 region, so initially tested BAC transgene containing full-length version with reporter insertion. Contrary our expectation, this failed To understand why, moved embryonic stem cell system without cassette. Despite being separated other genes, also different species, was XCI, suggesting that integration disrupted or critical elements. We refined escape-essential sequences only including promoter, exon 1 contiguous 1.6 first intron, consistent previous studies demonstrating local elements sufficient for escape. Interestingly, dual copy insertions showed higher escape, while drivers size number can boost inactive X

Язык: Английский

---

The molecular underpinnings of female predominance in lupus

Trends in Molecular Medicine, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Язык: Английский

---