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Title: Automated mass spectrometry imaging of over 2000 proteins from tissue sections at 100-µm spatial resolution

Journal Article · · Nature Communications

Biological tissues exhibit complex spatial heterogeneity that directs the functions of multicellular organisms. Quantifying protein expression is essential for elucidating processes within complex biological assemblies. Imaging mass spectrometry (IMS) is a powerful emerging tool for mapping the spatial distribution of metabolites and lipids across tissue surfaces, but technical challenges have limited the application of IMS to the analysis of proteomes. Methods for probing the spatial distribution of the proteome have generally relied on the use of labels and/or antibodies, which limits multiplexing and requires a priori knowledge of protein targets. Past efforts to make spatially resolved proteome measurements across tissues have had limited spatial resolution and proteome coverage and have relied on manual workflows. Here, we demonstrate an automated approach to imaging that utilizes label-free nanoproteomics to analyze tissue voxels, generating quantitative cell-type-specific images for >2000 proteins with 100-µm spatial resolution across mouse uterine tissue sections preparing for blastocyst implantation.

Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); March of Dimes
DOE Contract Number:
AC05-76RLO1830; SC0019620; R21-HD084788; UG3HL145593; R33-CA225248; R01HD068524; DA006668; 22-FY17- 889
OSTI ID:
1592415
Report Number(s):
PNNL-SA-138884
Journal Information:
Nature Communications, Vol. 11, Issue 1
Country of Publication:
United States
Language:
English

References (56)

Mass spectrometry in high-throughput proteomics: ready for the big time journal September 2010
Benchtop-compatible sample processing workflow for proteome profiling of < 100 mammalian cells journal November 2018
Sources of Technical Variability in Quantitative LC–MS Proteomics: Human Brain Tissue Sample Analysis journal April 2013
Subnanogram proteomics: Impact of LC column selection, MS instrumentation and data analysis strategy on proteome coverage for trace samples journal April 2018
Trp53 deficient mice predisposed to preterm birth display region-specific lipid alterations at the embryo implantation site journal September 2016
DAnTE: a statistical tool for quantitative analysis of -omics data journal May 2008
Uterine-specific p53 deficiency confers premature uterine senescence and promotes preterm birth in mice journal March 2010
Coordinated regulation of fetal and maternal prostaglandins directs successful birth and postnatal adaptation in the mouse journal August 2000
Three-dimensional imaging of lipids and metabolites in tissues by nanospray desorption electrospray ionization mass spectrometry journal November 2014
A statistical selection strategy for normalization procedures in LC-MS proteomics experiments through dataset-dependent ranking of normalization scaling factors journal November 2011
Spatially Resolved Proteome Profiling of <200 Cells from Tomato Fruit Pericarp by Integrating Laser-Capture Microdissection with Nanodroplet Sample Preparation journal August 2018
Quantitative mass spectrometry in proteomics: critical review update from 2007 to the present journal July 2012
Protein identification strategies in MALDI imaging mass spectrometry: a brief review journal February 2019
Proteomic Analysis of Single Mammalian Cells Enabled by Microfluidic Nanodroplet Sample Preparation and Ultrasensitive NanoLC-MS journal June 2018
A concise review of mass spectrometry imaging journal June 2010
Nanodroplet processing platform for deep and quantitative proteome profiling of 10–100 mammalian cells journal February 2018
Purified Wnt5a Protein Activates or Inhibits β-Catenin–TCF Signaling Depending on Receptor Context journal April 2006
Ultrasensitive proteome analysis using paramagnetic bead technology journal October 2014
High Recovery FASP Applied to the Proteomic Analysis of Microdissected Formalin Fixed Paraffin Embedded Cancer Tissues Retrieves Known Colon Cancer Markers journal July 2011
Mass spectrometry imaging for clinical research – latest developments, applications, and current limitations journal January 2017
Classification of HER2 Receptor Status in Breast Cancer Tissues by MALDI Imaging Mass Spectrometry journal April 2010
Optimized nLC-MS workflow for laser capture microdissected breast cancer tissue journal June 2012
Improved quality control processing of peptide-centric LC-MS proteomics data journal August 2011
Spatial proteomics: a powerful discovery tool for cell biology journal January 2019
Single-Cell Mass Spectrometry for Discovery Proteomics: Quantifying Translational Cell Heterogeneity in the 16-Cell Frog ( Xenopus ) Embryo journal January 2016
Protein biomarkers on tissue as imaged via MALDI mass spectrometry: A systematic approach to study the limits of detection journal May 2016
MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification journal November 2008
Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging journal December 2017
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
Quantitative Mass Spectrometry Imaging of Prostaglandins as Silver Ion Adducts with Nanospray Desorption Electrospray Ionization journal April 2018
Proteomic Analysis of Single Mammalian Cells Enabled by Microfluidic Nanodroplet Sample Preparation and Ultrasensitive NanoLC-MS journal June 2018
MALDI Imaging of Formalin-Fixed Paraffin-Embedded Tissues: Application to Model Animals of Parkinson Disease for Biomarker Hunting journal March 2008
Andromeda: A Peptide Search Engine Integrated into the MaxQuant Environment journal April 2011
A comparative analysis of computational approaches to relative protein quantification using peptide peak intensities in label-free LC-MS proteomics experiments journal November 2012
Tryptic Peptide Reference Data Sets for MALDI Imaging Mass Spectrometry on Formalin-fixed Ovarian Cancer Tissues journal December 2012
Spatially-Resolved Proteomics: Rapid Quantitative Analysis of Laser Capture Microdissected Alveolar Tissue Samples journal December 2016
Appropriate Crypt Formation in the Uterus for Embryo Homing and Implantation Requires Wnt5a-ROR Signaling journal July 2014
Liquid Chromatography-Mass Spectrometry-based Quantitative Proteomics journal June 2011
Single-Cell Mass Spectrometry for Discovery Proteomics: Quantifying Translational Cell Heterogeneity in the 16-Cell Frog ( Xenopus ) Embryo journal January 2016
Spatial mapping of protein abundances in the mouse brain by voxelation integrated with high-throughput liquid chromatography-mass spectrometry journal February 2007
Imaging of Proteins in Tissue Samples Using Nanospray Desorption Electrospray Ionization Mass Spectrometry journal October 2015
MALDI FTICR IMS of Intact Proteins: Using Mass Accuracy to Link Protein Images with Proteomics Data journal April 2015
Quantitative mass spectrometry in proteomics: a critical review journal August 2007
Spatially Resolved Proteome Mapping of Laser Capture Microdissected Tissue with Automated Sample Transfer to Nanodroplets journal June 2018
Mass spectrometry-based proteomics journal March 2003
Imaging Mass Spectrometry Reveals Unique Protein Profiles during Embryo Implantation journal July 2008
PI4P/phosphatidylserine countertransport at ORP5- and ORP8-mediated ER-plasma membrane contacts journal July 2015
Protein identification by accurate mass matrix-assisted laser desorption/ionization imaging of tryptic peptides: Protein identification by accurate mass MALDI imaging of peptides journal August 2011
Improved quality control processing of peptide-centric LC-MS proteomics data text January 2011
Combined Statistical Analyses of Peptide Intensities and Peptide Occurrences Improves Identification of Significant Peptides from MS-Based Proteomics Data journal November 2010
Hepatitis C virus enhances Rubicon expression, leading to autophagy inhibition and intracellular innate immune activation journal September 2020
A Novel Pathway Involving Progesterone Receptor, 12/15-Lipoxygenase-derived Eicosanoids, and Peroxisome Proliferator-activated Receptor γ Regulates Implantation in Mice journal December 2003
On-tissue protein identification and imaging by MALDI-Ion mobility mass spectrometry journal March 2010
Combinatory approaches prevent preterm birth profoundly exacerbated by gene-environment interactions journal August 2013
Trelliscope: A system for detailed visualization in the deep analysis of large complex data conference October 2013

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