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On-tissue spatial proteomics integrating MALDI-MS imaging with shotgun proteomics reveals soy consumption-induced potential candidate markers in a fragile X syndrome mouse model

ABSTRACT: Soy-based diets are associated with increased seizures and autism. Thus, there is an acute need for unbiased protein biomarker identification in Fragile X syndrome (FXS) in response to soy consumption. Herein, we present a spatial proteomics approach integrating mass spectrometry imaging (MSI) with label-free proteomics in a mouse model of FXS to map the spatial distribution and quantify the levels of proteins in the hippocampus and hypothalamus brain regions. In total, 1,250 unique peptides were spatially resolved, demonstrating the diverse array of peptidomes present in the tissue slices and the broad coverage of the strategy. A group of proteins that are known to be involved in glycolysis and synaptic transmission has been identified. The co-expression network analysis indicated that proteins in the soy-based diet group were significantly associated with metabolism and synapse modules in the Fmr1KO brain. Ultimately, this spatial proteomics work is a step toward identifying potential candidate protein markers and novel therapeutic targets for FXS

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Parkinson's Disease,Neuroblastoma

SUBMITTER: Min Ma

LAB HEAD: Lingjun Li

PROVIDER: PXD034326 | Pride | 2024-02-11

REPOSITORIES: Pride

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			Action	DRS
	04_HPC_R1.raw	Raw
	04_HPC_R2.raw	Raw
	04_HPC_R3.raw	Raw
	04_HPT_R1.raw	Raw
	04_HPT_R2.raw	Raw

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On-tissue spatial proteomics integrating MALDI-MS imaging with shotgun proteomics reveals soy consumption-induced biomarkers in a fragile X syndrome mouse model

Project description:Soy-based diets are associated with increased seizures and autism. Thus, there is an acute need for unbiased protein biomarker identification in Fragile X syndrome (FXS) in response to soy consumption. Herein, we present a spatial proteomics approach integrating mass spectrometry imaging (MSI) with label-free proteomics in a mouse model of FXS to map the spatial distribution and quantify the levels of proteins in the hippocampus and hypothalamus brain regions. In total, 1,004 unique peptides were spatially resolved, demonstrating the diverse array of peptidomes present on the tissue slices and the broad coverage of the strategy. A group of proteins that are known to be involved in the GABAergic system, synaptic transmission, and co-expression network analysis indicated that protein in soy group was significantly associated with metabolism and synapse modules in the Fmr1KO brain. Ultimately, this spatial proteomics work laid the ground for identifying novel therapeutic targets and biomarkers for FXS.

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Project description:Fragile X syndrome (FXS) is caused by the absence of the fragile X mental retardation protein (FMRP). We have previously generated FXS-induced pluripotent stem cells (iPSCs) from patients' fibroblasts. In this study, we aimed at unraveling the molecular phenotype of the disease. Our data revealed aberrant regulation of neural differentiation and axon guidance genes in FXS-derived neurons, which are regulated by the RE-1 silencing transcription factor (REST). Moreover, we found REST to be elevated in FXS-derived neurons. As FMRP is involved in the microRNA (miRNA) pathway we employed microRNA-array analyses and uncovered several miRNAs dysregulated in FXS-derived neurons. We found hsa-mir-382 to be down-regulated in FXS-derived neurons, and introduction of mimic-mir-382 into these neurons was sufficient to repress REST and up-regulate its axon guidance target genes. Our data link, FMRP and REST, through the miRNA pathway, and show a new aspect in the development of FXS. Affimetrix miRNA array of two WT and two fragile X syndrome derived neurons

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