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Hyaluronic acid networks and emergent tissue mechanics orchestrate mammalian limb regeneration

GSE274858 Mus musculus (mouse) Single-cell RNA-seq 11 samples Submitted 2026/02/04 Platform GPL24247
At a glance

Single-cell RNA-seq · mouse · 11 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
11 samples: 5 conditions, mostly in duplicateGroups 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
Hyaluronic acid and tissue mechanics orchestrate mammalian digit tip regenerationScience (New York, N.Y.) · 2026
Summary (written by the submitters)
In mammals, only distal amputations of the terminal digit regenerate, while more proximal ones result in non-regenerative, fibrotic scarring, underscoring the limits of our regenerative capacity. The mechanisms that direct one wound healing process over the other remain poorly understood. In this study, we investigated the role of cell-extrinsic cues, focusing upon the role of the extracellular matrix (ECM) and the bulk mechanical properties that arise from its composition.
Read the full summary ↓
Through single-cell RNA sequencing (scRNA-seq), we showed that non-regeneration and regeneration are differentially dominated by a select few mesenchymal cell sub-types that help determine the mechanical properties of their environment by synthesizing collagen remodeling proteins and glycosaminoglycans. In the regenerating blastema, we demonstrated that osteo-lineage cells deposit copious networks of hyaluronic acid (HA) and closely associated proteins, which corresponded with soft tissue mechanical properties. Using synthetic stiffness-tunable scaffolds, we further demonstrated that fibroblast-ECM feedback mechanisms exist, in which soft mechanical cues mimicking the blastema propagate the synthesis pro-regenerative ECM. Knockdown of HA networks critically impairs regeneration, promotes fibrotic viscoelastic mechanical properties, and enhances collagen fibrillogenesis. We further showed that stiffness affects regeneration by modulating the strength of early BMP signaling. Lastly, we stabilized the deposition of HA networks in vivo using Hyaluronic Acid and Proteoglycan Link Protein 1 (HAPLN1) to partially rescue non-regenerative amputations. Altogether, we showed that through feedback mechanisms, the ECM and emergent bulk tissue mechanics mediate mesenchymal cell activity during injury repair. These findings demonstrate that modulating the ECM microenvironment may augment restorative repair and inform future therapeutic strategies to overcome deficiencies in mammalian wound healing.
Published in
Hyaluronic acid and tissue mechanics orchestrate mammalian digit tip regeneration
Mui BWH, Wong JJY, Dumas CE et al. · Science (New York, N.Y.) 2026 · PMID 41955369 · doi:10.1126/science.ady3136
This dataset
Open GSE274858 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 GSE274858_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 PRJNA1148196 and SRA study SRP528178. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41955369) ↗
Study design
5 conditions, mostly in duplicate
Uninjured, P2, ×3 Regen, 14DPA, Control, ×2 Regen, 14DPA, 4MU treated, ×2 Non-regen, 14DPA, ×2 Uninjured, P3, ×2

Supports a case/control comparison: 2 samples read as cases, 2 as controls.

How we read this: 5 replicated groups read from 11 sample titles; they account for 11 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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