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Epigenetic Activation of SIRT6 Protects the Aging Intervertebral Disc

GSE320197 Mus musculus (mouse) Single-cell RNA-seq 20 samples Submitted 2026/03/04 Platform GPL24247
At a glance

Single-cell RNA-seq · mouse · 20 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. 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
20 samples: 5 × 24 months NP cells Vehicle control vs 5 × 24 months NP cells MDL-800 treated vs 5 × 24 months AF cells Vehicle Control vs 5 × 24 months AF cells MDL-800 treatedGroups 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)
Aging is one of the important risk factors for Intervertebral disc degeneration, a major contributor to chronic low back and neck pain. Our recent work has demonstrated a promising role for SIRT6, a nuclear NAD⁺- dependent deacetylase and defatty acylase, in maintaining intervertebral disc health with aging. We therefore investigated whether SIRT6 activation improves outcomes of disc health by studying the spinal phenotype of 24-month-old mice treated with a well-studied agonist, MDL-800, for 6 months.
Read the full summary ↓
Histological studies revealed healthy disc tissue morphology, enhanced cell viability, and lower degeneration scores in mice treated with MDL-800. Further mechanistic insights revealed that SIRT6 activation decreased H3K9ac levels, improved cell phenotype and matrix quality, and reduced the SASP burden in the disc, characterized by decreased abundance of p21, IL-6 and TGF-b. Tissue RNA-Seq, in vitro measurements of histone 3 modifications, and multi-omics ATAC-seq/RNA-seq analyses revealed that SIRT6 activation altered the epigenetic status (decreased H3K9ac, H3K36me3, and H3K79me2) and transcriptomic landscape of disc cells. Notably, MDL-800 treatment increased LC3II levels, indicating enhanced autophagic flux in nucleus pulposus cells. Furthermore, plasma LC-MS and NMR analyses revealed minimal systemic metabolic changes. ScRNA sequencing of splenocytes and bone marrow cells showed a decrease in the proportions of B cells, T cells, and granulocytes, without an altered systemic cytokine profile, indicating good tolerance and the absence of systemic inflammation following MDL-800 treatment. Our study demonstrates that SIRT6 activation modulates autophagy and cell senescence in the disc, underscoring the feasibility of targeting SIRT6 activation as a promising pharmacological strategy to maintain disc health in the aging spine.
This dataset
Open GSE320197 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 GSE320197_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 PRJNA1427130 and SRA study SRP678738. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
5 × 24 months NP cells Vehicle control vs 5 × 24 months NP cells MDL-800 treated vs 5 × 24 months AF cells Vehicle Control vs 5 × 24 months AF cells MDL-800 treated

Supports a case/control comparison: 10 samples read as cases, 10 as controls.

How we read this: 4 replicated groups read from 20 sample titles; they account for 20 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
Datasets on a similar topic

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