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Hypoxia Sensing in Resident Cardiac Macrophages Regulates Monocyte Fate Specification following Ischemic Heart Injury

GSE251991 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2024/09/02 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 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
Mus musculus (mouse)
Samples
16 samples
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)
Myocardial infarction initiates cardiac remodeling and is central to heart failure pathogenesis. Following myocardial ischemia reperfusion injury, monocytes enter the heart and differentiate into diverse subpopulations of macrophages. The mechanisms and dynamics of monocyte differentiation within this context are unknown. We investigated the role of macrophage hypoxia sensing on monocyte differentiation following reperfused myocardial infarction.
Read the full summary ↓
We show that deletion of Hif1α, a hypoxia response transcription factor, in resident cardiac macrophages led to increased remodeling and overrepresentation of a macrophage subset marked by arginase 1 (Arg1) expression. Arg1+ macrophages displayed an inflammatory gene signature and were predicted to represent an intermediate state within the monocyte differentiation cascade. Lineage tracing of Arg1+ macrophages revealed the existence of a monocyte differentiation trajectory consisting of multiple transcriptionally distinct macrophage states. We further showed that deletion of Hif1α in resident cardiac macrophages resulted in arrested progression through this trajectory and accumulation of an inflammatory intermediate state marked by persistent Arg1 expression. Depletion of the Arg1+ trajectory also results in increased heart remodeling following ischemic injury, likely due to the beneficial effects of macrophages downstream of Arg1+ macrophage differentiation. Collectively, our findings unveil distinct trajectories of monocyte differentiation and identify hypoxia sensing as an important determinant of monocyte differentiation following myocardial infarction.
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 GSE251991_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 PRJNA1056278 and SRA study SRP479834. Searching any of these in the dataset finder brings you back here.

Samples in this study

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+ 16 more — browse all 16 samples with per-sample file links →

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