Single-cell transcriptomic architecture and cellular communication circuits of parametrial adipose tissue in pregnant mice

Abstract

AimsThe activity and interactions of cellular subpopulations in the adipose tissue microenvironment are critical for the coordination of local and systemic adaptation during pregnancy. With a particular interest in parametrial adipose tissue (PmAT), single-cell RNA-sequencing (scRNA-seq) was utilized to unveil the gestative cellular composition and functional shift. Materials and methodsTo identify cell-type-enriched transcriptome profiles, a total of 18,074 cells in adipose tissue were studied. The cell populations were cataloged, and signaling crosstalk between adipocytes and other composition factions via soluble and membrane-bound factors were evaluated. Key findingsA marked decline of pregnancy adipocytes and relative elevation of non-adipocyte fractions were observed. A subpopulation of adipocytes, Adipo_5, with unique properties in the response to estrogen and the embryonic processes involved in pregnancy, was defined. Interactome analysis revealed the potential contribution of PmAT to the establishment of maternal-fetal immune tolerance. During gestation, adipocytes shut down outgoing signaling, resulting in deterioration of the resistin-related incoming signaling network in B cells, which would therefore benefit tissue-specific maternal-fetal tolerance. Furthermore, a subpopulation of adipocytes, Aipo_2, was also considered to take part in a paradigm shift in the process of pregnancy-induced chemical stiffness-triggered vesicular remodeling via the THBS signaling pathway network. SignificanceThese data-derived findings will encourage investigation into the role of pregnant PmTA in pregnancy-related immunological, hypertensive and metabolic disorders, with the ultimate goal of establishing preventive strategies to mitigate these pregnancy-related health challenges. This translational aspect of our work holds significant promise for improving maternal and fetal well-being.