GEO series

A multi-omics census reveals miRNA miR-let-7 as instigator of paternal mitochondrial dysfunction and in epigenetic heredity of intergenerational metabolic decline [PeWA]

GSE280277 Mus musculus (mouse) Single-cell RNA-seq 12 samples Submitted 2025/01/15 Platform GPL24247

At a glance

Single-cell RNA-seq · mouse · 12 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. 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: 12 samples: 4 × PeWA_NegativeControl vs 4 × PeWA_Let7d vs 4 × PeWA_Let7eGroups 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.

Summary (written by the submitters)

We describe that diet-induced obesity and weight loss development in male mice causes reversible abnormalities in glucose and lipid metabolism, serum metabolomes, and adipose tissue and liver gene expression and causes specific, but reversible, reductions in activity of genes controlling mitochondrial energy dissipation in white adipose tissue.

Read the full summary ↓

When mating obese mice with isogenic lean females, we observed highly concordant reductions in mitochondrial gene expression and translation in offspring that resemble those observed in obese fathers. When mapping small RNA responses across somatic and gametic cell types and between generations, we saw that obesity and weight loss reversible affected miRNA abundance, and observed several miR-let7 isoforms induced in obese adipose tissues of the paternal (F0) and offspring (F1) generation, as well as in sperm of F0 mice. Mechanistically, when overexpressing miR-let-7 in primary adipocytes, we found it to silence DICER1, a key rheostat required for adipose tissue adaptation in obesity as evidenced by functional deficiency in mitochondrial functioon following DICER1 loss. Upon ectopic delivery of miR-let7d/e levels into fertilized oocytes by microinjection, we elicited glucose intolerance and impairments in adipose mitochondrial gene expression in mice sired from miRNA-injected embryos, thus phenocopying key aspects of paternal obesity itself. When performing single-cell RNA-Seq in embryos, we found that miR-let7d/e delivery impaired mitochondrial gene expression, suggesting altered energy metabolism following sperm-mediated changes in zygotic miRNA pools. When studying miRNA alterations in human gametes, we found that lifestyle-induced weight loss downregulated MIR-LET7D/E in semen from human subjects, suggesting similar roles for human miR-let7d/e in gametic epigenomes and embryogenesis.

This dataset

Open GSE280277 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 GSE280277_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 PRJNA1177510 and SRA study SRP540715. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

4 × PeWA_NegativeControl vs 4 × PeWA_Let7d vs 4 × PeWA_Let7e

Supports a between-group comparison across 12 samples.

How we read this: 3 replicated groups read from 12 sample titles; they account for 12 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

GSM8593931 PeWA_NegativeControl1 PeWA_NegativeControl
GSM8593932 PeWA_NegativeControl2 PeWA_NegativeControl
GSM8593933 PeWA_Let7d1 PeWA_Let7d
GSM8593934 PeWA_Let7d2 PeWA_Let7d
GSM8593935 PeWA_Let7e1 PeWA_Let7e
GSM8593936 PeWA_Let7e2 PeWA_Let7e
GSM8593937 PeWA_NegativeControl3 PeWA_NegativeControl
GSM8593938 PeWA_NegativeControl4 PeWA_NegativeControl
GSM8593939 PeWA_Let7d3 PeWA_Let7d
GSM8593940 PeWA_Let7d4 PeWA_Let7d
GSM8593941 PeWA_Let7e3 PeWA_Let7e
GSM8593942 PeWA_Let7e4 PeWA_Let7e

Datasets on a similar topic

GSE280273 A multi-omics census reveals miRNA miR-let-7 as instigator of paternal mitochondrial dysfunction and in epigenetic heredity of intergenerational metabolic decline [F0_Liv_eWAT_RNAseq] 36 samples shares mir-let-7, intergenerational, mitochondrial, multi-omics, dysfunction, instigator, epigenetic, paternal
GSE280278 A multi-omics census reveals miRNA miR-let-7 as instigator of paternal mitochondrial dysfunction and in epigenetic heredity of intergenerational metabolic decline 279 samples shares mir-let-7, intergenerational, mitochondrial, multi-omics, dysfunction, instigator, epigenetic, paternal
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GSE289641 Noncanonical PRC2 chromatin association reveals a key role of EZHIP in intergenerational epigenetic memory transition [RNA-Seq] 68 samples shares intergenerational, epigenetic
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GSE293219 Adipocyte-specific Mlkl knockout mitigates obesity-induced metabolic dysfunction by enhancing mitochondrial functions. 36 samples shares mitochondrial, dysfunction
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