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SLC38A2 mediates selective L-serine influx across the blood-brain barrier and controls brain D-serine and excitatory synapse development

GSE330116 Mus musculus (mouse) RNA-seq (gene expression) 20 samples Submitted 2026/08/04 Platform GPL30172
At a glance

RNA-seq (gene expression) · mouse · 20 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
20 samples: 20 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
L-Serine is essential for brain metabolism, serving as a precursor for the synthesis of the neuromodulator D-serine, glycine, and lipids. Contrary to the prevailing view that brain L-serine is derived exclusively from local synthesis, our findings demonstrate that dietary L-serine is required to maintain brain L-serine levels and the production of its downstream metabolites.
Read the full summary ↓
Sphingolipidome analysis indicates that dietary restriction of serine/glycine leads to the formation of neurotoxic 1-deoxysphingolipids and affects the expression of circadian and endothelial cell genes in the hippocampus. We identified the glutamine transporter SLC38A2 as a selective L-serine transporter at the BBB that mediates the influx of circulating L-serine to the brain. Endothelial-selective Slc38a2 knockout (Slc38a2-cKO) decreased in vivo blood-to-brain L-serine influx and selectively lowered hippocampal L-serine and D-serine in mouse pups. Isotope tracing experiments confirmed reduced incorporation of L-serine into the brain of Slc38a2-cKO pups but revealed normal incorporation of L-glutamine, indicating that SLC38A2 does not use L-glutamine at this age. Serine-to-glycine conversion in Slc38a2-cKO pups was preserved, while the de novo synthesis of glycine from glucose was higher in the cerebral cortex. Slc38a2-cKO pups exhibited ultrastructural defects at excitatory synapses, including reduced synaptic vesicle cluster size and decreased postsynaptic density area. Immunoelectron microscopy demonstrated that SLC38A2 is localized to both the luminal and abluminal endothelial membranes, supporting a dual role for this transporter at the BBB. Luminal SLC38A2 appears to serve as a selective route for L-serine transport across the BBB during early postnatal development and is required for excitatory synapse maturation. In contrast, abluminal SLC38A2 is more consistent with a role in the equilibrative efflux of brain-derived SLC38A2 substrates. SLC38A2 inhibition may be beneficial for limiting D-serine accumulation in the brain, particularly in conditions with pathologically elevated D-serine levels, such as traumatic brain injury, epilepsy, and neurodegenerative disorders.
This dataset
Open GSE330116 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE330116_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1462775 and SRA study SRP698060. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
20 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 20 sample titles: 20 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
Datasets on a similar topic

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