Proteomics

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An integrated transcriptomic and proteomic map of the mouse hippocampus at synaptic resolution


ABSTRACT: Understanding the brain’s molecular diversity requires spatially resolved maps of transcripts and proteins across regions and compartments. Here, we performed deep spatial molecular profiling of the mouse hippocampus, combining microdissection of 3 subregions and 4 strata with fluorescence-activated synaptosome sorting, transcriptomics, and proteomics. This approach revealed thousands of locally enriched molecules spanning diverse receptor, channel, metabolic, and adhesion families. Integration of transcriptome and proteome data highlighted proteins tightly linked to or decoupled from mRNA availability, in part due to protein half-life differences. Incorporation of translatome data identified roles for protein trafficking versus local translation in establishing compartmental organization of pyramidal neurons, with distal dendrites showing increased reliance on local protein synthesis. Classification of CA1 synapses revealed contributions from kinases, cytoskeletal elements, and adhesion molecules in defining synaptic specificity. Together, this study provides a molecular atlas of the hippocampus and its synapses (syndive.org), and offers insights into spatial transcript-protein relationships.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Julian Langer  

LAB HEAD: Julian Langer

PROVIDER: PXD054879 | Pride | 2025-08-28

REPOSITORIES: Pride

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An integrated transcriptomic and proteomic map of the mouse hippocampus at synaptic resolution.

Kaulich Eva E   Waselenchuk Quinn Q   Fürst Nicole N   Desch Kristina K   Mosbacher Janus J   Ciirdaeva Elena E   Juengling Marcel M   Ray Roshni R   Nassim-Assir Belquis B   Tushev Georgi G   Langer Julian D JD   Schuman Erin M EM  

Nature communications 20250826 1


Understanding the brain's molecular diversity requires spatially resolved maps of transcripts and proteins across regions and compartments. Here, we performed deep spatial molecular profiling of the mouse hippocampus, combining microdissection of 3 subregions and 4 strata with fluorescence-activated synaptosome sorting, transcriptomics, and proteomics. This approach revealed thousands of locally enriched molecules spanning diverse receptor, channel, metabolic, and adhesion families. Integration  ...[more]

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