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Transcriptomics of S3 segment in mice: response to type 1 diabetes, SGLT1/2 inhibition, or GLP1 receptor agonism response to type 1 diabetes, SGLT1/2 inhibition or GLP1 receptor agonism

GSE325466 Mus musculus (mouse) RNA-seq (gene expression) 54 samples Submitted 2026/06/01 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 54 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
54 samples: 54 × S3-LCMGroups 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.
Paper
Transcriptomics of S3 segment in mice: response to type 1 diabetes, SGLT1/2 inhibition, or GLP1 receptor agonismAmerican journal of physiology. Renal physiology · 2026
Summary (written by the submitters)
Inhibitors of SGLT2 (SGLT2i) and diabetes enhance glucose delivery and reabsorption in late proximal tubule S3 segments. However, the molecular consequences remain poorly understood. Here we determined transcriptomic changes in S3 segments of male adult DBA wildtype (WT) and littermate diabetic Akita mice ± Sglt1 knockout (Sglt1-KO) given vehicle or SGLT2i dapagliflozin for 2 weeks, and in Akita mice receiving GLP1R agonist (GLP1RA) semaglutide.
Read the full summary ↓
RNA sequencing was performed in S3 segments isolated by immunostaining-guided laser-capture-microdissection in deep cortex/outer medulla. Among 19,068 detected annotated genes, 838 genes were differentially expressed by SGLT2i in WT (DEGs; p<0.05) and 1,410 genes in Akita vs. WT. ~34% of SGLT2i-sensitive genes changed in same direction in Akita. Both maneuvers upregulated pathways of cellular proliferation (confirmed by phospho-Ser10 Histone H3 staining) and cellular response to stress, while downregulating pathways of immune/inflammatory response, cytokine production/receptor signaling, and cell adhesion/migration. Both maneuvers also induced unique responses. Unique pathway responses to SGLT2i in WT included increase in DNA dealkylation/demethylation and lysosomal acidification, and reduced valine biosynthesis. Differences in Sglt1-dependency of responses to Akita versus SGLT2i in WT suggested different initiating mechanisms. In Akita mice, inhibition of SGLT2, Sglt1-KO and GLP1R agonism restored 12, 18 and 25% of DEGs, respectively. Akita downregulated whole kidney SGLT1 membrane expression, potentially to limit glucose-induced stress. GLP1RA reduced/restored cellular stress response and proliferation in Akita in S3 segments, associated with enhanced/restored kidney membrane expression of SGLT1. Finally, Akita-sensitive genes unresponsive to any of the 3 maneuvers were identified that may indicate new therapeutic avenues.
Published in
Transcriptomics of S3 segment in mice: response to type 1 diabetes, SGLT1/2 inhibition, or GLP1 receptor agonism
Kim YC, Meng C, Kanoo S et al. · American journal of physiology. Renal physiology 2026 · PMID 42213650 · doi:10.1152/ajprenal.00109.2026
This dataset
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.

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 GSE325466_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1440221 and SRA study SRP685344. Searching any of these in the dataset finder brings you back here.

Study design
54 × S3-LCM

Supports a between-group comparison across 54 samples.

How we read this: 1 replicated groups read from 54 sample titles; they account for 54 of them. 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

+ 14 more — browse all 54 samples with per-sample file links →

Datasets on a similar topic

Search all mouse RNA-seq datasets in GEO →

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