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Endothelial and systemic upregulation of miR-34a-5p fine-tunes senescence in progeria

GSE272195 Mus musculus (mouse) Non-coding RNA profiling 36 samples Submitted 2024/07/13 Platform GPL13112
At a glance

Non-coding RNA profiling · mouse · 36 samples

What it is
Non-coding RNA profilingLevels of RNAs that do not code for proteins, such as miRNA or lncRNA.
Organism
Mus musculus (mouse)
Samples
36 samples: 12 conditions, mostly in triplicateGroups 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
Endothelial and systemic upregulation of miR-34a-5p fine-tunes senescence in progeriaAging · 2022
Summary (written by the submitters)
Endothelial defects significantly contribute to cardiovascular pathology in the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). Using an endothelium-specific progeria mouse model, we identify a novel, endothelium-specific microRNA (miR) signature linked to the p53-senescence pathway and a senescence-associated secretory phenotype (SASP).
Read the full summary ↓
Progerin-expressing endothelial cells exert profound cell-non-autonomous effects initiating senescence in non-endothelial cell populations and causing immune cell infiltrates around blood vessels. Comparative miR expression analyses revealed unique upregulation of senescence-associated miR34a-5p in endothelial cells with strong accumulation at atheroprone aortic arch regions but also, in whole cardiac- and lung tissues as well as in the circulation of progeria mice. Mechanistically, miR34a-5p knockdown reduced not only p53 levels but also late-stage senescence regulator p16 with no effect on p21 levels, while p53 knockdown reduced miR34a-5p and partially rescued p21-mediated cell cycle inhibition with a moderate effect on SASP. These data demonstrate that miR34a-5p reinforces two separate senescence regulating branches in progerin-expressing endothelial cells, the p53- and p16-associated pathways, which synergistically maintain a senescence phenotype that contributes to cardiovascular pathology. Thus, the key function of circulatory miR34a-5p in endothelial dysfunction-linked cardiovascular pathology offers novel routes for diagnosis, prognosis and treatment for cardiovascular aging in HGPS and potentially geriatric patients. This research was supported by by the Austrian Science Fund grant [P 32595 /Grant DOI: 10.55776/P32595] to Selma Osmanagic-Myers, and (I 4694-B) to Roland Foisner, the latter under the frame of EJP RD, the European Joint Programme on Rare Diseases. In addition, this project has received funding from the European Union’s Horizon 2020 research and innovation programme under the EJP RD COFUND-EJP N 825575. https://www.doi.org/10.55776/P32595
Published in
Endothelial and systemic upregulation of miR-34a-5p fine-tunes senescence in progeria
Manakanatas C, Ghadge SK, Agic A et al. · Aging 2022 · PMID 35020601 · doi:10.18632/aging.203820
This dataset
Open GSE272195 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 GSE272195_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 ↗

Also filed as BioProject PRJNA1135490 and SRA study SRP519740. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 35020601) ↗
Study design
12 conditions, mostly in triplicate
WT endothelial cells, ×3 LA-Tg endothelial cells, ×3 Prog-Tg endothelial cells, ×3 WT endothelial cells, microRNA, ×3 LA-Tg endothelial cells, microRNA, ×3 Prog-Tg endothelial cells, microRNA, ×3 WT endothelial cell supernatant, microRNA, ×3 LA-Tg endothelial supernatant, microRNA, ×3 +4 more

Supports a between-group comparison across 36 samples.

How we read this: 12 replicated groups read from 36 sample titles; they account for 36 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
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