Single-Cell and Spatial Multi-Omics Reveal Estrogen-Mediated Vaginal Wall Microenvironment Remodeling and a Perivascular Reparative Niche in Postmenopausal Pelvic Organ Prolapse

To resolve this, we employed high-definition spatial transcriptomics, achieving a near-cellular resolution map of the postmenopausal vaginal wall. This spatial atlas reveals spatial patterns underlying estrogen’s action, the spatial organization of a structured HAS1+ fibroblast-pericyte cellular unit around vasculature.

Estrogen is associated with the recruitment of TWIST1-related HAS1+ fibroblasts into this precise micro-anatomical location, enabling their functional coupling with pericytes. This co-localization facilitates a rewired fibroblast-pericyte signaling axis, enhancing intercellular communication. Computational pharmacology further suggests this unit as a potential druggable functional module.