GEO series

A Humanized Monoclonal Antibody Targeting an Ectonucleotidase Rescues Heart Function after Myocardial Infarction

GSE255826 Mus musculus (mouse) Single-nucleus RNA-seq 10 samples Submitted 2024/10/14 Platform GPL24247

At a glance

Single-nucleus RNA-seq · mouse · 10 samples

What it is: Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). 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: 10 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)

We have recently demonstrated that the ectonucleotidase ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) is upregulated in the heart after myocardial infarction (MI) and initiates an aberrant metabolic cascade that worsens cell death and heart repair. Genetic loss of function approaches demonstrated that animals deficient in ENPP1 exhibited enhanced heart repair and had significantly superior post MI heart function.

Read the full summary ↓

Whether human ENPP1 protein can be therapeutically targeted after heart injury remains unknown. Here, we engineer a humanized monoclonal antibody targeting human ENPP1 (hENPP1mAb) and demonstrate high affinity and specificity of binding to the catalytic domain of human ENPP1. In mice, genetically engineered, to express the human ENPP1 ortholog instead of murine ENPP1 (humanized ENPP1 mice), we demonstrate that administration of hENPP1mAb significantly rescued post MI heart function compared to IgG injected animals. Using metabolomics, single nuclear transcriptomics, and cellular respiration assays, we demonstrate that administration of the hENPP1mAb induces organ wide metabolic and transcriptional reprogramming of the heart that enhances myocyte cellular respiration and decreases cell death and fibrosis in the infarcted heart. Biodistribution and safety studies with radiolabeled hENPP1mAb showed specific organ wide distribution without any organ toxicity. Finally, in humanized ENPP1 animals that have also been genetically engineered to exhibit antibody clearance kinetics similar to humans, we demonstrate that a single "shot" of the hENPP1mAb after MI is sufficient to rescue post infarct cardiac dysfunction. Taken together our observations provide proof of concept on how the human ectonucleotidase ENPP1 can be therapeutically targeted to prevent heart failure after MI.

This dataset

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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 GSE255826_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 PRJNA1076596 and SRA study SRP489786. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Samples in this study

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+ 10 more — browse all 10 samples with per-sample file links →

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