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NAD+ prevents chronic kidney disease by activating renal tubular metabolism - bulk RNA-sequencing

GSE261869 Mus musculus (mouse) Single-nucleus RNA-seq 32 samples Submitted 2025/03/10 Platform GPL24247
At a glance

Single-nucleus RNA-seq · mouse · 32 samples

What it is
Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Mus musculus (mouse)
Samples
32 samples: 8 conditions, mostly with about 4 replicates eachGroups 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
NAD+ prevents chronic kidney disease by activating renal tubular metabolismJCI insight · 2025
Summary (written by the submitters)
Chronic kidney disease (CKD) is associated with renal metabolic disturbances, including impaired fatty acid oxidation (FAO). Nicotinamide adenine dinucleotide (NAD+) is a small molecule that participates in hundreds of metabolism-related reactions. NAD+ levels are decreased in CKD, and NAD+ supplementation is protective. However, both the mechanism of how NAD+ supplementation protects from CKD, as well as the cell types involved, are poorly understood.
Read the full summary ↓
Using a mouse model of Alport syndrome, we show that nicotinamide riboside (NR), an NAD+ precursor, stimulates renal peroxisome proliferator-activated receptor α signaling and restores FAO in the proximal tubules, thereby protecting from CKD in both sexes. Bulk RNA-sequencing shows that renal metabolic pathways are impaired in Alport mice and activated by NR in both sexes. These transcriptional changes are confirmed by orthogonal imaging techniques and biochemical assays. Single nuclei RNA-sequencing and spatial transcriptomics, both the first of their kind from Alport mice, show that NAD+ supplementation restores FAO in proximal tubule cells. Finally, we also report, for the first time, sex differences at the transcriptional level in this Alport model. In summary, the data herein identify a nephroprotective mechanism of NAD+ supplementation in CKD, and they demonstrate that this benefit localizes to the proximal tubule cells.
Published in
NAD+ prevents chronic kidney disease by activating renal tubular metabolism
Jones BA, Gisch DL, Myakala K et al. · JCI insight 2025 · PMID 40059824 · doi:10.1172/jci.insight.181443
This dataset
Open GSE261869 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 GSE261869_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1088395 and SRA study SRP495401. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40059824) ↗
Study design
8 conditions, mostly with about 4 replicates each
Kidney cortex, male, control, vehicle, ×4 Kidney cortex, male, control, nicotinamide ri… ×4 Kidney cortex, male, Alport, vehicle, ×4 Kidney cortex, male, Alport, nicotinamide rib… ×4 Kidney cortex, female, control, vehicle, ×4 Kidney cortex, female, control, nicotinamide … ×4 Kidney cortex, female, Alport, vehicle, ×4 Kidney cortex, female, Alport, nicotinamide r… ×4

Supports a between-group comparison across 32 samples.

How we read this: 8 replicated groups read from 32 sample titles; they account for 32 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
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