GEO series

Determine the role of ALK5 signaling in human brain pericytes treated with TGFβ.

GSE269066 Homo sapiens (human) RNA-seq (gene expression) 16 samples Submitted 2024/06/30 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 16 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: Homo sapiens (human)
Samples: 16 samples: 4 × Scr PC, no treatment vs 4 × Scr PC, TGFβ vs 4 × siALK5 PC, no treatment vs 4 × siALK5 PC, TGFβGroups 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: Loss of TGFβ-Mediated Repression of Angiopoietin-2 in Pericytes Underlies Germinal Matrix Hemorrhage PathogenesisStroke · 2024

Summary (written by the submitters)

Pericytes (PCs) are microvascular mural cells which constituent the embryonic blood brain barrier (BBB) along with endothelial cells (ECs). During brain development, germinal matrix (GM) - a highly vascularized region rich in neuronal-glial precursors, is selectively vulnerable to hemorrhage in premature infants. The transforming growth factor β (TGFβ) pathway plays a crucial role in barrier development by regulating cellular cross talk between PCs and ECs.

Read the full summary ↓

Indeed, murine embryos lacking TGFβ receptor activin receptor-like kinase 5 (Alk5) in brain PCs (mutants) develop gross germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) and culminate in perinatal lethality. Mutant GM vessels display reduced PC and collagen coverage, abnormal vessel dilation and EC hyperproliferation. However, the mechanistic link between PC-specific deletion of ALK5 and aberrant EC behavior remains elusive. Herein, using bulk RNA sequencing from human brain PCs lacking ALK5 (siALK5) as well as murine vascular cells [PCs and ECs] isolated from embryonic brain at embryonic days E11.5 and E13.5 we establish that angiopoietin 2 (ANGPT2), a secreted angiogenic growth factor, is robustly repressed by the TGFβ pathway in PCs. Conversely, mutants lacking PC-ALK5 secrete higher levels of ANGPT2 resulting in overactivation of tyrosine protein kinase receptor (TIE2) and culminating in EC hyperproliferation, vessel dilation, BBB breakdown and GMH. PC-specific Angpt2 deletion or pharmacological inhibition in mutants improves GM vessel morphology, reduces EC proliferation and attenuates GMH pathogenesis. Taken together, we demonstrate that loss of TGFβ-mediated ANGPT2 repression in PCs is detrimental for BBB integrity and identify ANGPT2 as an important pathological target for GMH-IVH.

Published in

Loss of TGFβ-Mediated Repression of Angiopoietin-2 in Pericytes Underlies Germinal Matrix Hemorrhage Pathogenesis

Dave JM, Chakraborty R, Agyemang A et al. · Stroke 2024 · PMID 39129597 · doi:10.1161/STROKEAHA.123.045248

This dataset

Open GSE269066 in finder → Find more human 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 GSE269066_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 PRJNA1120049 and SRA study SRP511782. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39129597) ↗

Study design

4 × Scr PC, no treatment vs 4 × Scr PC, TGFβ vs 4 × siALK5 PC, no treatment vs 4 × siALK5 PC, TGFβ

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 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

GSM8305806 Scr PC, no treatment 1 Scr PC, no treatment
GSM8305807 Scr PC, no treatment 2 Scr PC, no treatment
GSM8305808 Scr PC, no treatment 3 Scr PC, no treatment
GSM8305809 Scr PC, no treatment 4 Scr PC, no treatment
GSM8305810 Scr PC, TGFβ 1 Scr PC, TGFβ
GSM8305811 Scr PC, TGFβ 2 Scr PC, TGFβ
GSM8305812 Scr PC, TGFβ 3 Scr PC, TGFβ
GSM8305813 Scr PC, TGFβ 4 Scr PC, TGFβ
GSM8305814 siALK5 PC, no treatment 1 siALK5 PC, no treatment
GSM8305815 siALK5 PC, no treatment 2 siALK5 PC, no treatment
GSM8305816 siALK5 PC, no treatment 3 siALK5 PC, no treatment
GSM8305817 siALK5 PC, no treatment 4 siALK5 PC, no treatment
GSM8305818 siALK5 PC, TGFβ 1 siALK5 PC, TGFβ
GSM8305819 siALK5 PC, TGFβ 2 siALK5 PC, TGFβ
GSM8305820 siALK5 PC, TGFβ 3 siALK5 PC, TGFβ
GSM8305821 siALK5 PC, TGFβ 4 siALK5 PC, TGFβ

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