Imaging Mass Spectrometry Reveals Unique Protein Profiles during Embryo Implantation

Burnum, Kristin E.; Tranguch, Susanne; Mi, Deming; Daikoku, Takiko; Dey, Sudhansu K.; Caprioli, Richard M.

doi:10.1210/en.2008-0309

Cited by 64 publications

(51 citation statements)

References 15 publications

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“…The mouse epididymis has been imaged to identify proteins in specific regions of the organ that may be involved in spermatozoa maturation (25). Developmental studies have been carried out involving the maturation of mouse prostate (26) and the implantation process of the mouse embryo (27). A major focus of protein imaging has been in the area of cancer (8,10,23,(28)(29)(30)(31) where studies have been carried out to improve molecular classification of grade, help predict clinical outcome, and examine molecular tumor margins.…”

Section: Histology-directed Ms Profilingmentioning

confidence: 99%

Molecular imaging of proteins in tissues by mass spectrometry

Seeley

Caprioli

2008

Proc. Natl. Acad. Sci. U.S.A.

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272

239

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Imaging MS (IMS) is an emerging technology that permits the direct analysis and determination of the distribution of molecules in tissue sections. Biological molecules such as proteins, peptides, lipids, xenobiotics, and metabolites can be analyzed in a highthroughput manner with molecular specificity not readily achievable through other means. Tissues are analyzed intact and thus spatial localization of molecules within a tissue is preserved. Several studies are presented that focus on the unique types of information obtainable by IMS, such as A␤ isoform distributions in Alzheimer's plaques, protein maps in mouse brain, and spatial protein distributions in human breast carcinoma. The analysis of a biopsy taken 100 years ago from a patient with amyloidosis illustrates the use of IMS with formalin-fixed tissues. Finally, the registration and correlation of IMS with MRI is presented.MALDI ͉ molecular histology P rotein analysis is a vital part of the process of investigation and understanding of human disease. The expression of proteins in terms of both qualitative and quantitative aspects, structure, modifications, protein-protein and protein-liquid interactions, spatial distribution, and temporal behavior all constitute essential aspects of the study of proteins. Several commonly used technologies that can assess these various aspects of protein structure and function include 2D gel electrophoresis, MS, and fluorescence-and affinitybased techniques. However, as studies progress and more complex and detailed questions are asked at the molecular level, it is clear that new enabling approaches are needed that transcend the limitations of current technologies. In this article, we describe our own current work involving the study of proteins using imaging and profiling MALDI MS in the analysis of tissue sections. This is not a review of the field of imaging MS (IMS) (see ref. 1 for such a review). MS TechnologyThe use of MS for the molecular image analysis of samples has been known for decades for the analysis of elements and small organic molecules. Secondary ion MS and laser desorption MS have been effectively used in this manner for Ͼ20 years (2). However, these techniques have not been effective for the image analysis of polypeptides and proteins.Direct analysis of tissues of biological and clinical interest using MALDI MS has been shown to be successful for the study of the mid-to low molecular weight proteome. Because this technology analyzes intact tissue, avoiding homogenization and separation steps, the spatial distribution of molecules within the tissue is preserved. The process is relatively simple in that a matrix (typically a small aromatic organic molecule dissolved in an organic solvent) is deposited on top of a tissue section followed by irradiation with a laser (e.g., nitrogen, 337 nm or Nd:YAG, 355 nm). Molecules are subsequently desorbed and ionized (3). MALDI is often coupled with TOF mass analyzers in which ions are accelerated at a fixed potential, traverse a field free drift region (flight tube...

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Section: Histology-directed Ms Profilingmentioning

confidence: 99%

Molecular imaging of proteins in tissues by mass spectrometry

Seeley

Caprioli

2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

272

239

View full text Add to dashboard Cite

show abstract

“…MALDI imaging mass spectrometry (IMS) generates ion density maps from tissue sections that allow protein and phospholipid localization to be visualized without prior knowledge of the specifi c molecules being analyzed (19)(20)(21)(22)(23)(24)(25)(26)(27). This technology has been previously used to analyze proteins involved in proliferation, differentiation, and apoptosis during early mouse pregnancy, providing unique and distinctive proteomic profi les of implantation sites ( 28 ). In this study, phospholipid distribution was visualized using the molecular imaging mode of both MALDI-TOF/TOF (time-offl ight) and MALDI Fourier transform ion cyclotron resonance (FTICR) mass spectrometers.…”

Section: Maldi-ms Datamentioning

confidence: 99%

Spatial and temporal alterations of phospholipids determined by mass spectrometry during mouse embryo implantation

Burnum

Cornett

Puolitaival

et al. 2009

Journal of Lipid Research

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150

141

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Early pregnancy failure often arises due to defects that occur before, during, or immediately after implantation. Even with in vitro fertilization and embryo-transfer techniques, implantation rates remain low in humans, most often as a result of embryos being transferred into nonreceptive uteri ( 1 ). Studying the molecular interactions that regulate implantation will provide a better understanding of these signaling pathways, eventually leading to new approaches to prevent implantation failure.There is evidence that phospholipid metabolism and signaling infl uences early pregnancy events ( 2 ). Phospholipids are vital structural and regulatory components of biological membranes and serve as precursors for many active biomolecules, such as eicosanoids and lysophospholipids ( 3, 4 ). Prostaglandins, one major group of eicosanoid lipid molecules, are produced from arachidonic acid (AA) that is released from membrane phospholipids by phospholipase A 2 . The released AA is acted upon by cyclooxygenases (COXs) to form prostaglandin H 2 , which is then converted to various prostaglandins by specifi c

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“…Previously, using MALDI-IMS and DESI, the molecular profiles during embryo development were performed on the tissue sections or preimplantation embryos (17)(18)(19)(20). In an attempt to investigate the early development of the CNS, a mouse embryo was flashfrozen and sectioned at embryonic day (E) 15.5 after fertilization at the lumbar level of the developing spinal cord.…”

Section: Significancementioning

confidence: 99%

Microscopy ambient ionization top-down mass spectrometry reveals developmental patterning

Hsu¹,

White

Hayashi

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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There is immense cellular and molecular heterogeneity in biological systems. Here, we demonstrate the utility of integrating an inverted light microscope with an ambient ionization source, nanospray electrospray desorption ionization, attached to a highresolution mass spectrometer to characterize the molecular composition of mouse spinal cords. We detected a broad range of molecules, including peptides and proteins, as well as metabolites such as lipids, sugars, and other small molecules, including S-adenosyl methionine and glutathione, through top-down MS. Top-down analysis revealed variation in the expression of Hb, including the transition from fetal to adult Hb and heterogeneity in Hb subunits consistent with the genetic diversity of the mouse models. Similarly, temporal changes to actin-sequestering proteins β-thymosins during development were observed. These results demonstrate that interfacing microscopy with ambient ionization provides the means to perform targeted in situ ambient top-down mass spectral analysis to study the pattern of proteins, lipids, and sugars in biologically heterogeneous samples.

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Imaging Mass Spectrometry Reveals Unique Protein Profiles during Embryo Implantation

Cited by 64 publications

References 15 publications

Molecular imaging of proteins in tissues by mass spectrometry

Molecular imaging of proteins in tissues by mass spectrometry

Spatial and temporal alterations of phospholipids determined by mass spectrometry during mouse embryo implantation

Microscopy ambient ionization top-down mass spectrometry reveals developmental patterning

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