Lipidomics reveals dramatic lipid compositional changes in the maturing postnatal lung

Dautel, Sydney E.; Kyle, Jennifer; Clair, Gérémy; Sontag, Ryan; Weitz, Karl K.; Shukla, Anil; Nguyen, Son; Kim, Young Mo; Zink, Erika; Luders, Teresa; Frevert, Charles W.; Gharib, Sina A.; Laskin, Julia; Carson, James P.; Metz, Thomas O.; Corley, Richard A.; Ansong, Charles

doi:10.1038/srep40555

Cited by 72 publications

(75 citation statements)

References 67 publications

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“…Detailed lipidomics characterization of adult mouse lung tissue revealed elevated levels of long chain polyunsaturated fatty acids and LPC species in adult mice in comparison with pups. [34] This observation was attributed to a greater state of inflamation of adult lungs maintained in a healthy state through a fine balance between pro-inflamatory and pro-resolution lipids and associated protein mediators.…”

Section: Resultsmentioning

confidence: 99%

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Towards High-Resolution Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry Coupled to Shear Force Microscopy

Nguyen

Sontag

Carson³

et al. 2017

J. Am. Soc. Mass Spectrom.

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Constant mode ambient mass spectrometry imaging (MSI) of tissue sections with high lateral resolution of better than 10 μm was performed by combining shear force microscopy with nanospray desorption electrospray ionization (nano-DESI). Shear force microscopy enabled precise control of the distance between the sample and nano-DESI probe during MSI experiments and provided information on sample topography. Proof-of-concept experiments were performed using lung and brain tissue sections representing spongy and dense tissues, respectively. Topography images obtained using shear force microscopy were comparable to the results obtained using contact profilometry over the same region of the tissue section. Variations in tissue height were found to be dependent on the tissue type and were in the range of 0–5 μm for lung tissue and 0–3 μm for brain tissue sections. Ion images of phospholipids obtained in this study are in good agreement with literature data. Normalization of nano-DESI MSI images to the signal of the internal standard added to the extraction solvent allowed us to construct high-resolution ion images free of matrix effects.

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Section: Resultsmentioning

confidence: 99%

“…In our recent lipidomics study, these PC species have been also observed as abundant components of lung tissue. [34]…”

Section: Resultsmentioning

confidence: 99%

Towards High-Resolution Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry Coupled to Shear Force Microscopy

Nguyen

Sontag

Carson³

et al. 2017

J. Am. Soc. Mass Spectrom.

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“…The data were normalized using global median centering, in which each sample was scaled by the median of its observed abundance values. This approach has been described previously 104–107 and utilized in a number of other studies 108–110 . Lipids were evaluated using analysis of variance (ANOVA) with a Dunnett test correction to compare infected to mock at each timepoint (24 hours and 48 hpi).…”

Section: Methodsmentioning

confidence: 99%

A global lipid map defines a network essential for Zika virus replication

Leier

Weinstein

Kyle

et al. 2020

Preprint

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26Zika virus (ZIKV), an arbovirus of global concern, remodels intracellular membranes to form 27 replication sites. How ZIKV dysregulates lipid networks to allow this, and consequences for 28 disease, is poorly understood. Here, we performed comprehensive lipidomics to create a lipid 29 network map during ZIKV infection. We found that ZIKV significantly alters host lipid 30 composition, with the most striking changes seen within subclasses of sphingolipids. Ectopic 31 expression of ZIKV NS4B protein resulted in similar changes, demonstrating a role for NS4B in 32 modulating sphingolipid pathways. Disruption of sphingolipid biosynthesis in various cell types, 33including human neural progenitor cells, blocked ZIKV infection. Additionally, the sphingolipid 34 ceramide redistributes to ZIKV replication sites and increasing ceramide levels by multiple 35 pathways sensitizes cells to ZIKV infection. Thus, we identify a sphingolipid metabolic network 36 with a critical role in ZIKV replication and show that ceramide flux is a key mediator of ZIKV 37 infection. Results 112 ZIKV alters the lipid landscape of host cells 113To understand how cellular lipid metabolism is altered by ZIKV infection, we carried out 114 a global lipidomic survey of the model Huh7 human hepatic carcinoma cell line 20 infected for 24 115 or 48 hours with Asian lineage ZIKV strain FSS13025 (Fig. 1a). Lipids extracted from 116 populations of mock and infected cells (n = 5 biological replicates per condition) were analyzed 117 with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) (Supplementary Data 118 1 and Supplementary Fig. 1a-f). We identified 340 lipid species spanning the phospholipid, 119 sphingolipid, glycerolipid, and sterol classes for which pairwise comparisons of normalized 120 abundance between mock and infected cells could be made (Supplementary Data 1). Of these, 121 80 species (23.5%) showed significant changes in abundance by 24 hours post-infection (hpi) 122 and 172 species (50.6%) were significantly altered by 48 hpi (P < 0.05, ANOVA or g-test) 123( Supplementary Data 1). Principal component analysis (PCA) of these observations confirmed 124 that infection status (mock or ZIKV) and timepoint (24 or 48 hpi) accounted most of these 125 changes, with changes in lipid composition between mock and infected cells increasing over 126 time (Fig. 1b). 127Next, we examined how ZIKV-induced changes in host lipid composition broke down by 128 subclass and species (Fig. 1c, d). A map of the pairwise correlations of all 340 species at 48 hpi 129 ( Supplementary Fig. 2a) revealed that lipid subclasses largely fell into two groups of species 130 that were either enriched or depleted in abundance ( Supplementary Fig. 2b), suggesting that 131 individual metabolic pathways are up-or down-regulated to create a specific lipid milieu around 132 the events of the viral replication cycle. Supporting this, many of the trends we observed were 133 consistent with earlier reports of functional roles for lipids during flavivirus infection. In ...

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“…Lipidomic analysis was performed on BALF at PNNL as previously described (52). Proteomics analysis was performed on BALF at Pacific Northwest Laboratory using a label-free approach (53) as detailed in Supplemental Methods.…”

Section: Methodsmentioning

confidence: 99%