PNNL

Abstract

The placenta is a complex and heterogeneous organ that links the mother and fetus, playing a crucial role in nourishing, supporting the growth, and protecting the fetus throughout pregnancy. Integrative spatial multi-omics approaches can provide a systems level understanding of changes associated with histological variations of the placenta during healthy pregnancy and pregnancy complications. Herein, we built upon our previously developed metabolome-informed proteome imaging (MIPI) workflow to enhance applicability for biomedical imaging investigations, such as characterization of human placenta tissue heterogeneity. We advanced our MIPI workflow to include lipidomic imaging, along with expanding the scope of metabolomic imaging by incorporating on-tissue chemical derivatization (OTCD). Lipidome imaging of 12-µm-thick placenta sections identified subtle molecular differences between two morphologically distinct compartments of a placental villi functional unit, syncytiotrophoblast (STB) and core. Next, our advanced metabolome imaging mapped villi functional units with enriched metabolomic activities related to steroid and lipid metabolism, outlining distinct molecular distributions across morphologically different villi compartments. Complementary proteome imaging on these villi functional units revealed a plethora of fatty acid- and steroid-related enzymes uniquely distributed in STB and core compartments. Integration across our advanced MIPI imaging modalities enabled us to reconstruct active biological pathways of molecular synthesis and maternal-fetal signaling across morphologically distinct placental villi compartments, STB and core, with the micrometer-scale resolution.