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Comparison of transcriptomic profiles between HFPO-DA and positive controls for PPARa, PPARg or cytotoxicity in mouse, rat, and pooled human hepatocytes

GSE248251 Homo sapiens (human) RNA-seq (gene expression) 1100 samples Submitted 2024/04/30 Platform GPL17021Platform GPL18694Platform GPL24247Platform GPL16791
At a glance

RNA-seq (gene expression) · human · 1100 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
1100 samples: 119 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
Comparison of transcriptomic profiles between HFPO-DA and prototypical PPARα, PPARγ, and cytotoxic agents in mouse, rat, and pooled human hepatocytesToxicological sciences : an official journal of the Society of Toxicology · 2024
Summary (written by the submitters)
Like many per- or polyfluorinated alkyl substances (PFAS), toxicity studies with HFPO-DA (ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate; CASRN 62037-80-3), a short-chain PFAS used in the manufacture of some types of fluorinated polymers, indicate that the liver is the primary target of toxicity in rodents following oral exposure.
Read the full summary ↓
Although the current weight of evidence supports the PPARa mode of action (MOA) for liver effects in HFPO-DA-exposed mice, alternate MOAs have also been hypothesized including PPARg or cytotoxicity. To further evaluate the MOA for HFPO-DA in rodent liver, transcriptomic analyses were conducted on samples from primary mouse, rat and pooled human hepatocytes treated for 12, 24 or 72 hours with various concentrations of HFPO-DA, or established agonists of PPARa (GW7647), PPARg (rosiglitazone), or cytotoxic agents (i.e., acetaminophen or d-galactosamine). Concordance analyses of enriched pathways across chemicals within each species demonstrated greatest concordance between HFPO-DA and PPARa agonist GW7647-treated hepatocytes compared to the other chemicals evaluated. These findings were supported by benchmark concentration modeling and predicted upstream regulator results. In addition, transcriptomic analyses across species demonstrated a greater transcriptomic response in rodent hepatocytes treated with HFPO-DA or agonists of PPARa or PPARg, indicating rodent hepatocytes are more sensitive to HFPO-DA or PPARa/g agonist treatment. These results are consistent with previously published transcriptomic analyses and further support that liver effects in HFPO-DA-exposed rodents are mediated through rodent-specific PPARa signaling mechanisms as part of the MOA for PPARa activator-induced rodent hepatocarcinogenesis.
Published in
Comparison of transcriptomic profiles between HFPO-DA and prototypical PPARα, PPARγ, and cytotoxic agents in mouse, rat, and pooled human hepatocytes
Heintz MM, Klaren WD, East AW et al. · Toxicological sciences : an official journal of the Society of Toxicology 2024 · PMID 38574381 · doi:10.1093/toxsci/kfae044
This dataset
Open GSE248251 in finder → Find more 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 GSE248251_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: 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 PRJNA1043110 and SRA study SRP473039. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38574381) ↗
Study design
119 conditions, mostly in triplicate
mouse_CD-1_GW7647_24_0.01_uM_A ×4 mouse_CD-1_HFPO_DA_24_0.1_uM_F ×4 mouse_CD-1_Rosiglitzone_24_0.01_uM_B ×4 mouse_CD-1_Rosiglitzone_24_0.1_uM_C ×4 mouse_CD-1_Acetominophen_24_0.3_mM_G ×4 mouse_CD-1_Acetominophen_24_1_mM_H ×4 mouse_CD-1_GW7647_24_1_uM_D ×4 mouse_CD-1_Rosiglitzone_24_1_uM_D ×4 +112 more

Supports a between-group comparison across 399 samples.

How we read this: 119 replicated groups read from the first 400 of 1100 sample titles; they account for 399 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

+ 1060 more — browse all 1100 samples with per-sample file links →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.