|Sex Chromosomes and Gonads Shape the Sex-Biased Transcriptomic Landscape in Tlr7-Mediated Demyelination During Aging.
|Year of Publication
|Lopez-Lee C, Kodama L, Fan L, Wong MYing, Foxe NR, Jiaz L, Yu F, Ye P, Zhu J, Norman K, Torres ERuth, Kim RD, Mousa GAlzaem, Dubal D, Liddelow S, Luo W, Gan L
|2023 Sep 21
Demyelination occurs in aging and associated diseases, including Alzheimer's disease. Several of these diseases exhibit sex differences in prevalence and severity. Biological sex primarily stems from sex chromosomes and gonads releasing sex hormones. To dissect mechanisms underlying sex differences in demyelination of aging brains, we constructed a transcriptomic atlas of cell type-specific responses to illustrate how sex chromosomes, gonads, and their interaction shape responses to demyelination. We found that sex-biased oligodendrocyte and microglial responses are driven by interaction of sex chromosomes and gonads prior to myelin loss. Post demyelination, sex chromosomes mainly guide microglial responses, while gonadal composition influences oligodendrocyte signaling. Significantly, ablation of the X-linked gene Toll-like receptor 7 (Tlr7), which exhibited sex-biased expression during demyelination, abolished the sex-biased responses and protected against demyelination.
|PubMed Central ID
|R01 AG054214 / AG / NIA NIH HHS / United States
R01 AG072758 / AG / NIA NIH HHS / United States
R01 AG074541 / AG / NIA NIH HHS / United States
U54 NS100717 / NS / NINDS NIH HHS / United States