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GPR124 regulates murine CNS angiogenesis and blood-brain barrier formation by an intracellular domain-independent mechanism

GSE225367 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2024/04/19 Platform GPL17021
At a glance

RNA-seq (gene expression) · mouse · 12 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
12 samples: 3 × Gpr124-/- bEC E15.5 ME vs 2 × WT bECs E15.5 JE vs 2 × Gpr124ΔC/ΔC bEC E15.5 JE vs 2 × Gpr124ΔC/ΔC bEC E15.5 LEGroups 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
GPR124 regulates murine brain embryonic angiogenesis and BBB formation by an intracellular domain-independent mechanismDevelopment (Cambridge, England) · 2024
Summary (written by the submitters)
The GPR124/RECK/WNT7 pathway essentially regulates central nervous system angiogenesis and blood-brain barrier (BBB) function. GPR124, a brain endothelial adhesion 7-pass transmembrane protein, associates with membrane RECK, which binds and stabilizes newly synthesized WNT7 for subsequent transfer to Frizzled (FZD) and canonical b-catenin signaling.
Read the full summary ↓
GPR124 function remains enigmatic; while its extracellular domain (ECD) is required, the poorly conserved intracellular domain (ICD) appears to be variably required in mammals versus zebrafish, potentially mediated by bridging of the GPR124 and FZD ICDs by intracellular adaptor proteins. GPR124 ICD deletion mutants impair zebrafish angiogenesis, but paradoxically still mediate WNT7 signaling upon mammalian cell transfection. We thus further investigated the GPR124 C-terminal ICD by deletion in mice (Gpr124ΔC). Notably, Gpr124ΔC/ΔC mice could be born and did not recapitulate Gpr124-/- embryonic lethal forebrain hemorrhage. GPR124ΔC protein was inefficiently expressed, resulting in mild, hypomorphic, non-hemorrhagic defects in CNS angiogenesis and BBB function, sparing the cortex and only confined to ganglionic eminences. Impaired surface expression of GPR124ΔC directly correlated with reduced endothelial WNT signaling, arguing against an intrinsic signaling deficiency. Further, GPR124ΔC and recombinant GPR124 ECD both rescued WNT7 signaling following brain endothelial Gpr124 knockdown. Thus, in mice, the GPR124 essential regulation of WNT7-dependent CNS forebrain angiogenesis and BBB function is exerted by ICD-independent functionality, extending the range of signaling mechanisms used by adhesion 7-pass transmembrane receptors.
Published in
GPR124 regulates murine brain embryonic angiogenesis and BBB formation by an intracellular domain-independent mechanism
Yuki K, Vallon M, Ding J et al. · Development (Cambridge, England) 2024 · PMID 38682276 · doi:10.1242/dev.202794
This dataset
Open GSE225367 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 GSE225367_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 PRJNA935353 and SRA study SRP422796. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38682276) ↗
Study design
3 × Gpr124-/- bEC E15.5 ME vs 2 × WT bECs E15.5 JE vs 2 × Gpr124ΔC/ΔC bEC E15.5 JE vs 2 × Gpr124ΔC/ΔC bEC E15.5 LE

Supports a between-group comparison across 9 samples.

How we read this: 4 replicated groups read from 12 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
Datasets on a similar topic

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