Journal Article

Advanced multi-modal mass spectrometry imaging reveals functional differences of placental villous compartments at microscale resolution

Burnum-Johnson, Kristin E., Fillmore, Thomas L., Bramer, Lisa M., Zemaitis, Kevin J., Gao, Yuqian, Wu, Ruonan, Piehowski, Paul D., Williams, Sarah M., Kadam, Leena, Kim, Joonhoon, Veličković, Marija, Monroe, Matthew E., Moore, Ronald J., Myatt, Leslie, Veličković, Dušan, Orton, Daniel

2025

Overview

The placenta is a complex and heterogeneous organ that links the mother and fetus, playing a crucial role in nourishing and protecting the fetus throughout pregnancy. Integrative spatial multi-omics approaches can provide a systems-level understanding of molecular changes underlying the mechanisms leading to the histological variations of the placenta during healthy pregnancy and pregnancy complications. Herein, we advance our metabolome-informed proteome imaging (MIPI) workflow to include lipidomic imaging, while also expanding the molecular coverage of metabolomic imaging by incorporating on-tissue chemical derivatization (OTCD). The improved MIPI workflow advances biomedical investigations by leveraging state-of-the-art molecular imaging technologies. Lipidome imaging identifies molecular differences between two morphologically distinct compartments of a placental villous functional unit, syncytiotrophoblast (STB) and villous core. Next, our advanced metabolome imaging maps villous functional units with enriched metabolomic activities related to steroid and lipid metabolism, outlining distinct molecular distributions across morphologically different villous compartments. Complementary proteome imaging on these villous functional units reveals a plethora of fatty acid- and steroid-related enzymes uniquely distributed in STB and villous core compartments. Integration across our advanced MIPI imaging modalities enables the reconstruction of active biological pathways of molecular synthesis and maternal-fetal signaling across morphologically distinct placental villous compartments with micrometer-scale resolution. Spatial multi-omics methodologies are essential for capturing the molecular heterogeneity of complex biological systems. In this study, the authors introduce a multi-omics imaging workflow capable of mapping metabolite-protein interactions with spatial specificity, enabling pathway-level resolution across distinct placental tissue microenvironments.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 60 APPLIED LIFE SCIENCES / 631/136 / 631/45/320 / 631/45/475 / 82/58 / Biological analysis / Chemical synthesis / Chorionic Villi - diagnostic imaging / Chorionic Villi - metabolism / Compartments / Female / Fetuses / Heterogeneity / Humanities and Social Sciences / Humans / Imaging / Lipid Metabolism / Lipidomics - methods / Lipids / Mass spectrometry / Mass Spectrometry - methods / Mass spectroscopy / Metabolites / Metabolome / Metabolomics / Metabolomics - methods / Microenvironments / Molecular Imaging - methods / multidisciplinary / Peptide mapping / Placenta / Placenta - diagnostic imaging / Placenta - metabolism / Pregnancy / Pregnancy complications / Protein interaction / Proteome - metabolism / Proteomes / Proteomics - methods / Science / Science (multidisciplinary) / Steroids / Trophoblasts - metabolism / Workflow