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PI3Kα inhibition blocks osteochondroprogenitor specification and the hyper-inflammatory response to prevent heterotopic ossification

GSE237512 Homo sapiens (human) RNA-seq (gene expression) 39 samples Submitted 2024/05/05 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 39 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
39 samples: 10 conditions, mostly with about 4 replicates eachGroups 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
PI3Kα inhibition blocks osteochondroprogenitor specification and the hyper-inflammatory response to prevent heterotopic ossificationeLife · 2025
Summary (written by the submitters)
Heterotopic ossification (HO) occurs following mechanical trauma, burns, or congenitally in patients suffering from fibrodysplasia ossificans progressiva (FOP). Recently, we demonstrated that inhibitors of phosphatidyl-inositol 3-kinase alpha (PI3Kα), including the already marketed BYL719/Alpelisib/Piqray, may become a useful therapy for patients undergoing HO.
Read the full summary ↓
In this study, we have confirmed these results and optimized the timing of administration of BYL719. We found that BYL719 effectively prevents HO when administered even up to three to seven days after injury. We demonstrate in cell cultures and in a mouse model of HO, that the major actions of BYL719 are on-target effects through inhibition of PI3Kα, without directly affecting ACVR1/ALK2 kinase activity. In vivo, we found that lack of PI3Kα in progenitors at injury sites is sufficient to prevent HO. Moreover, time course assays in HO lesions demonstrate that BYL719 not only blocks osteochondroprogenitor specification, but also reduces the inflammatory response. BYL719 inhibits the migration, the proliferation, and the expression of pro-inflammatory cytokines in monocytes and mast cells, suggesting that BYL719 hampers the hyper-inflammatory status of HO lesions. As part of this study, we have conducted bulk RNA sequencing using human mesenchymal stem cells (hMSCs) expressing ACVR1/ALK2-R206H to assess molecular effectors driving the therapeutic potential of BYL719 in FOP. Altogether, these results highlight the potential of PI3Kα inhibition as a safe and effective therapeutic strategy for HO.
Published in
PI3Kα inhibition blocks osteochondroprogenitor specification and the hyper-inflammatory response to prevent heterotopic ossification
Valer JA, Deber A, Wits M et al. · eLife 2025 · PMID 40525393 · doi:10.7554/eLife.91779
This dataset
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.

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 GSE237512_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA995559 and SRA study SRP449875. Searching any of these in the dataset finder brings you back here.

Study design
10 conditions, mostly with about 4 replicates each
hMSC R206H, DMSO, Activin A, ×4 hMSC R206H, BYL719, Activin A, ×4 hMSC WT, DMSO, Vehicle, ×4 hMSC WT, DMSO, BMP6, ×4 hMSC WT, BYL719, BMP6, ×4 hMSC WT, DMSO, Activin A, ×4 hMSC WT, BYL719, Activin A, ×4 hMSC R206H, DMSO, BMP6, ×4 +2 more

Supports a between-group comparison across 39 samples.

How we read this: 10 replicated groups read from 39 sample titles; they account for 39 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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