GEO series

PARK7/DJ-1 deficiency modulates microglial activation in response to LPS-induced inflammation

GSE254687 Mus musculus (mouse) Single-cell RNA-seq 19 samples Submitted 2024/08/09 Platform GPL24247

At a glance

Single-cell RNA-seq · mouse · 19 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: 19 samples: 19 samples, each with a distinct title — no replicated groupsGroups 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: PARK7/DJ-1 deficiency impairs microglial activation in response to LPS-induced inflammationJournal of neuroinflammation · 2024

Summary (written by the submitters)

Background: Specific microglia responses are thought to contribute to the development and progression of neurodegenerative diseases, including Parkinson’s disease (PD). However, the phenotypic acquisition of microglial cells and their role during the underlying neuroinflammatory processes remain largely elusive.

Read the full summary ↓

Here, according to the multiple-hit hypothesis, which stipulates that PD etiology is determined by a combination of genetics and various environmental risk factors, we investigate microglial transcriptional programs and morphological adaptations under PARK7/DJ-1 deficiency, a genetic cause of PD, during lipopolysaccharide (LPS)-induced inflammation. Methods: Using a combination of single-cell RNA-sequencing, bulk RNA-sequencing, multicolor flow cytometry and immunofluorescence analyses, we comprehensively compared microglial cell phenotypic characteristics in PARK7/DJ-1 knock-out (KO) with wildtype littermate mice following 6- or 24-hour intraperitoneal injection with LPS. In a translational approach, we conducted corresponding analyses in human PARK7/DJ-1 mutant induced pluripotent stem cell (iPSC)-derived microglia and murine bone marrow-derived macrophages (BMDMs). Results: By excluding the contribution of other immune brain resident and peripheral cells, we show that microglia acutely isolated from PARK7/DJ-1 KO mice display a distinct phenotype, specially related to type II interferon and DNA damage response signaling, when compared with wildtype microglia, in response to LPS. We also detected discrete signatures in human PARK7/DJ-1 mutant iPSC-derived microglia and BMDMs from PARK7/DJ-1 KO mice. These specific transcriptional signatures were reflected at the morphological level, with microglia in LPS-treated PARK7/DJ-1 KO mice showing a less amoeboid cell shape compared to wildtype mice, both at 6 and 24 hours after acute inflammation, as also observed in BMDMs. Conclusions: Taken together, our results show that, under inflammatory conditions, PARK7/DJ-1 deficiency skews microglia towards a distinct phenotype characterized by downregulation of genes involved in type II interferon signaling and a less prominent amoeboid morphology compared to wildtype microglia. These findings suggest that the underlying oxidative stress associated with the lack of PARK7/DJ-1 affects microglia neuroinflammatory responses, which may play a causative role in PD onset and progression.

Published in

PARK7/DJ-1 deficiency impairs microglial activation in response to LPS-induced inflammation

Lind-Holm Mogensen F, Sousa C, Ameli C et al. · Journal of neuroinflammation 2024 · PMID 39014482 · doi:10.1186/s12974-024-03164-x

This dataset

Open GSE254687 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 GSE254687_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 PRJNA1071524 and SRA study SRP487079. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39014482) ↗

Study design

19 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 19 sample titles: 19 distinct titles with little repetition. 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

GSM8048782 M_KO_LPS_1 [554_M_KO_LPS_S18]
GSM8048783 M_KO_LPS_2 [562_M_KO_LPS_S22]
GSM8048784 M_KO_LPS_3 [568_M_KO_LPS_S23]
GSM8048785 M_KO_LPS_4 [586_M_KO_LPS_S24]
GSM8048786 M_KO_LPS_5 [645_M_KO_LPS_S29]
GSM8048787 M_KO_PBS_1 [556_M_KO_PBS_S19]
GSM8048788 M_KO_PBS_2 [559_M_KO_PBS_S20]
GSM8048789 M_KO_PBS_3 [561_M_KO_PBS_S21]
GSM8048790 M_KO_PBS_4 [579_M_KO_PBS_S27]
GSM8048791 M_KO_PBS_5 [644_M_KO_PBS_S28]
GSM8048792 M_WT_LPS_1 [531_M_WT_LPS_S12]
GSM8048793 M_WT_LPS_2 [551_M_WT_LPS_S15]
GSM8048794 M_WT_LPS_3 [552_M_WT_LPS_S16]
GSM8048795 M_WT_LPS_4 [581_M_WT_LPS_S26]
GSM8048796 M_WT_LPS_5 [634_M_WT_LPS_S30]
GSM8048797 M_WT_PBS_1 [534_M_WT_PBS_S13]
GSM8048798 M_WT_PBS_2 [553_M_WT_PBS_S17]
GSM8048799 M_WT_PBS_3 [557_M_WT_PBS_S14]
GSM8048800 M_WT_PBS_4 [600_M_WT_PBS_S25]

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