GEO series

Modulation of non-canonical WNT5B-NFATc2 pathway-dependent MMP14 expression in astrocytes ameliorates neuropathology and motor behaviors in Huntington's disease mice

GSE294445 Mus musculus (mouse) RNA-seq (gene expression) 9 samples Submitted 2026/05/31 Platform GPL13112

At a glance

RNA-seq (gene expression) · mouse · 9 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: 9 samples: 3 × WT-Control vs 3 × HD-Control vs 3 × HD-WNT5BGroups 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)

Huntington’s disease (HD) is a fatal neurodegenerative disorder characterized by a triad of behavioral symptoms, including involuntary movement, emotional change, and cognitive dysfunction. Although alterations in the WNT signaling pathway have been reported in HD, its precise role in disease pathogenesis remains unclear. In this study, we found that astrocytic WNT5B mRNA and protein levels were elevated in the striatum of both HD patients and HD mouse models.

Read the full summary ↓

WNT5B induced prolonged expression of matrix metallopeptidase 14 (MMP14), an extracellular matrix (ECM)-degrading enzyme, through NFATc2 transcription factor activation via the non-canonical WNT signaling pathway in both human and primary mouse astrocytes. The significant upregulation of MMP14 led to ECM degradation, medium spiny neuron (MSN) damage, and increased mutant huntingtin aggregation in N171-82Q HD transgenic mice. Furthermore, WNT5B gain-of-function exacerbated neuropathology, impaired motor coordination, and shortened the lifespan of N171-82Q mice. We further report that overexpression of estrogen receptor (ER ) suppresses NFATc2 transcriptional activity. Genistein, a phytoestrogen, reduced MMP14 transcription by antagonizing the NFATc2 pathway and prevented ECM degradation in N171-82Q mice. Additionally, genistein administration ameliorated motor behavior and prolonged the lifespan of N171-82Q mice. Together, our findings reveal a molecular pathological mechanism in which astrocytic MMP14 transcription, activated by the non-canonical WNT5B signaling pathway, causes ECM degradation, MSN damage, and accelerates neurodegeneration in HD. Modulation of non-cell-autonomous WNT5B-NFATc2-MMP14 pathway by genistein may serve as a potential therapeutic strategy for ameliorating HD pathogenesis.

This dataset

Open GSE294445 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 GSE294445_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 PRJNA1249471 and SRA study SRP577865. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

3 × WT-Control vs 3 × HD-Control vs 3 × HD-WNT5B

Supports a between-group comparison across 9 samples.

How we read this: 3 replicated groups read from 9 sample titles; they account for 9 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

GSM8905548 WT-Control-1 WT-Control
GSM8905550 WT-Control-2 WT-Control
GSM8905551 WT-Control-3 WT-Control
GSM8905553 HD-Control-1 HD-Control
GSM8905554 HD-Control-2 HD-Control
GSM8905555 HD-Control-3 HD-Control
GSM8905557 HD-WNT5B-1 HD-WNT5B
GSM8905558 HD-WNT5B-2 HD-WNT5B
GSM8905559 HD-WNT5B-3 HD-WNT5B

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