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

Journal Article · · Nature Communications
ORCiD logo [1];  [2]; ORCiD logo [1]; ORCiD logo [1];  [1]; ORCiD logo [1]; ORCiD logo [1];  [1]; ORCiD logo [1];  [1]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1];  [2]; ORCiD logo [1]
  1. Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
  2. Oregon Health & Science University, Portland, OR (United States)

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.

Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC05-76RL01830
OSTI ID:
2566019
Report Number(s):
PNNL-SA--201502
Journal Information:
Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 16; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

References (78)

Neurodevelopment and Metabolism in the Maternal-Placental-Fetal Unit journal May 2024
A statistical selection strategy for normalization procedures in LC-MS proteomics experiments through dataset-dependent ranking of normalization scaling factors journal November 2011
Multimodal mass spectrometry imaging identifies cell-type-specific metabolic and lipidomic variation in the mammalian liver journal April 2024
A multiscale model of placental oxygen exchange: The effect of villous tree structure on exchange efficiency journal November 2016
Omics-based approaches to guide the design of biomaterials journal April 2023
Comparison of Phospholipid Molecular Species between Terminal and Stem Villi of Human Term Placenta by Imaging Mass Spectrometry journal March 2010
Review: Human trophoblast fusion and differentiation: Lessons from trisomy 21 placenta journal February 2012
The Human Placenta Project: Placental structure, development, and function in real time journal May 2014
Differences of glycocalyx composition in the structural elements of placenta in preeclampsia journal July 2016
The endocrine function of human placenta: an overview journal January 2016
Metabolomics to understand placental biology: Where are we now? journal December 2021
High-Speed Tandem Mass Spectrometric in Situ Imaging by Nanospray Desorption Electrospray Ionization Mass Spectrometry journal September 2013
Mass Spectrometry Imaging for Dissecting Steroid Intracrinology within Target Tissues journal November 2013
Mass Spectrometry Spatial-Omics on a Single Conductive Slide journal January 2021
Simultaneous Multiplexed Imaging of Biomolecules in Transgenic Mouse Brain Tissues Using Mass Spectrometry Imaging: A Multi-omic Approach journal June 2022
Enhanced Spatial Mapping of Histone Proteoforms in Human Kidney Through MALDI-MSI by High-Field UHMR-Orbitrap Detection journal September 2022
Expanded Coverage of Phytocompounds by Mass Spectrometry Imaging Using On-Tissue Chemical Derivatization by 4-APEBA journal August 2023
MALDI-MSI-LC-MS/MS Workflow for Single-Section Single Step Combined Proteomics and Quantitative Lipidomics journal March 2024
Design and Performance of a Novel Interface for Combined Matrix-Assisted Laser Desorption Ionization at Elevated Pressure and Electrospray Ionization with Orbitrap Mass Spectrometry journal June 2017
Mass Spectrometry Imaging: A Review of Emerging Advancements and Future Insights journal December 2017
Multimodal Mass Spectrometry Imaging of Rat Brain Using IR-MALDESI and NanoPOTS-LC-MS/MS journal December 2021
Combined Statistical Analyses of Peptide Intensities and Peptide Occurrences Improves Identification of Significant Peptides from MS-Based Proteomics Data journal November 2010
FDR-controlled metabolite annotation for high-resolution imaging mass spectrometry journal November 2016
Placental mobilization of free fatty acids contributes to altered materno-fetal transfer in obesity journal February 2021
Placental transcriptomic signatures of prenatal and preconceptional maternal stress journal January 2024
Single-cell RNA-seq reveals the diversity of trophoblast subtypes and patterns of differentiation in the human placenta  journal July 2018
Automated mass spectrometry imaging of over 2000 proteins from tissue sections at 100-μm spatial resolution journal January 2020
Single-cell reconstruction of the early maternal–fetal interface in humans journal November 2018
Spatial multiomics map of trophoblast development in early pregnancy journal March 2023
A spatially resolved timeline of the human maternal–fetal interface journal July 2023
Single-nucleus multi-omic profiling of human placental syncytiotrophoblasts identifies cellular trajectories during pregnancy journal January 2024
Mapping microhabitats of lignocellulose decomposition by a microbial consortium journal February 2024
High spatial resolution imaging of biological tissues using nanospray desorption electrospray ionization mass spectrometry journal November 2019
Using clusterProfiler to characterize multiomics data journal July 2024
Single-cell transcriptional profiling reveals cellular and molecular divergence in human maternal–fetal interface journal June 2022
A comparative lipidomic study of the human placenta from women with or without gestational diabetes mellitus journal January 2022
The importance of placental lipid metabolism across gestation in obese and non-obese pregnancies journal January 2023
Placenta plays a critical role in maternal–fetal resource allocation journal September 2016
Improved quality control processing of peptide-centric LC-MS proteomics data journal August 2011
Hemochorial placentation: development, function, and adaptations† journal February 2018
Groups: knowledge spreadsheets for symbolic biocomputing journal January 2013
Spatial N-glycomics of the normal breast microenvironment reveals fucosylated and high-mannose N-glycan signatures related to BI-RADS density and ancestry journal June 2024
KEGG for taxonomy-based analysis of pathways and genomes journal October 2022
Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface journal February 2017
Human placental biology at single‐cell resolution: a contemporaneous review journal November 2021
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing journal January 1995
Human placental villi contain stromal macrovesicles associated with networks of stellate cells journal September 2019
A single-cell survey of the human first-trimester placenta and decidua journal October 2018
A genome scale transcriptional regulatory model of the human placenta journal June 2024
Pregnancy Ketonemia and Development of the Fetal Central Nervous System journal June 2018
Human type 2 17beta-hydroxysteroid dehydrogenase mRNA and protein distribution in placental villi at mid and term pregnancy journal July 2007
Computational prediction of human metabolic pathways from the complete human genome journal January 2004
Proteome profiling of human placenta reveals developmental stage-dependent alterations in protein signature journal August 2021
A proteomic profile of the healthy human placenta journal January 2023
Spatial and temporal alterations of phospholipids determined by mass spectrometry during mouse embryo implantation journal May 2009
Comparative Proteomics Analysis of Placenta from Pregnant Women with Intrahepatic Cholestasis of Pregnancy journal December 2013
Decrease in Sphingomyelin (d18:1/16:0) in Stem Villi and Phosphatidylcholine (16:0/20:4) in Terminal Villi of Human Term Placentas with Pathohistological Maternal Malperfusion journal November 2015
Protein N-Glycans in Healthy and Sclerotic Glomeruli in Diabetic Kidney Disease journal May 2024
A selective process for application of EDC and 4-APEBA for carbonyl containing metabolites by MALDI-MSI V.2 other June 2024
Integrated Proteomic and N-Glycoproteomic Profiling of Placental Tissues of Patients with Preeclampsia journal January 2023
Omics Approaches to Study Formation and Function of Human Placental Syncytiotrophoblast journal June 2021
Editorial: Multi-Omics Approaches to Study Placental Development and Disease journal November 2021
Maternal obesity alters the placental transcriptome in a fetal sex-dependent manner journal June 2023
The role of the annexin A protein family at the maternal–fetal interface journal March 2024
Innate Immune Mechanisms to Protect Against Infection at the Human Decidual-Placental Interface journal September 2020
Placenta: an old organ with new functions journal April 2024
Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta journal September 2018
Integrated Metabolomic and Lipidomic Analysis in the Placenta of Preeclampsia journal February 2022
LC-MS/MS untargeted lipidomics uncovers placenta lipid signatures from intrahepatic cholestasis of pregnancy journal June 2024
Proteomic Approaches in the Study of Placenta of Pregnancy Complicated by Gestational Diabetes Mellitus journal September 2022
Extra Purified Exosomes from Human Placenta Contain an Unpredictable Small Number of Different Major Proteins journal May 2019
Sphingolipid Signature of Human Feto-Placental Vasculature in Preeclampsia journal February 2020
Revisiting Steroidogenic Pathways in the Human Placenta and Primary Human Trophoblast Cells journal February 2021
Roles of Two Small Leucine-Rich Proteoglycans Decorin and Biglycan in Pregnancy and Pregnancy-Associated Diseases journal September 2021
Placental Lactogen as a Marker of Maternal Obesity, Diabetes, and Fetal Growth Abnormalities: Current Knowledge and Clinical Perspectives journal April 2020
Ceramides during Pregnancy and Obstetrical Adverse Outcomes journal November 2023
Spontaneous Unexplained Preterm Labor with Intact Membrane: Finding Protein Biomarkers through Placenta Proteome book September 2018
Imaging Mass Spectrometry: A Perspective journal April 2019