On-Tissue Spatial
Proteomics Integrating MALDI-MS
Imaging with Shotgun Proteomics Reveals Soy Consumption-Induced Protein
Changes in a Fragile X Syndrome Mouse Model
posted on 2023-12-18, 16:40authored byMin Ma, Qinying Yu, Daniel G. Delafield, Yusi Cui, Zihui Li, Miyang Li, Wenxin Wu, Xudong Shi, Pamela R. Westmark, Alejandra Gutierrez, Gui Ma, Ang Gao, Meng Xu, Wei Xu, Cara J. Westmark, Lingjun Li
Fragile X syndrome (FXS), the leading cause of inherited
intellectual
disability and autism, is caused by the transcriptional silencing
of the FMR1 gene, which encodes the fragile X messenger
ribonucleoprotein (FMRP). FMRP interacts with numerous brain mRNAs
that are involved in synaptic plasticity and implicated in autism
spectrum disorders. Our published studies indicate that single-source,
soy-based diets are associated with increased seizures and autism.
Thus, there is an acute need for an unbiased protein marker identification
in FXS in response to soy consumption. Herein, we present a spatial
proteomics approach integrating mass spectrometry imaging with label-free
proteomics in the FXS mouse model to map the spatial distribution
and quantify levels of proteins in the hippocampus and hypothalamus
brain regions. In total, 1250 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, synaptic transmission,
and coexpression network analysis suggest a significant association
between soy proteins and metabolic and synaptic processes in the Fmr1KO brain. Ultimately, this spatial proteomics
work represents a crucial step toward identifying potential candidate
protein markers and novel therapeutic targets for FXS.