Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 5:489:137515.
doi: 10.1016/j.jhazmat.2025.137515. Epub 2025 Feb 6.

Single-cell RNA sequencing reveals tissue-specific transcriptomic changes induced by perfluorooctanesulfonic acid (PFOS) in larval zebrafish (Danio rerio)

Kruuttika M Satbhai  1 , Emily S Marques  1 , Ravi Ranjan  2 , Alicia R Timme-Laragy  3
Affiliations

Single-cell RNA sequencing reveals tissue-specific transcriptomic changes induced by perfluorooctanesulfonic acid (PFOS) in larval zebrafish (Danio rerio)

Kruuttika M Satbhai et al. J Hazard Mater. .

Abstract

Perfluorooctanesulfonic acid (PFOS) elicits adverse effects on numerous organs and developmental processes but the mechanisms underlying these effects are not well understood. Here, we use single-cell RNA-sequencing to assess tissue-specific transcriptomic changes in zebrafish (Danio rerio) larvae exposed to 16 µM PFOS or dimethylsulfoxide (0.01 %) from 3-72 h post fertilization (hpf). Data analysis was multi-pronged and included pseudo-bulk, untargeted clustering, informed pathway queries, and a cluster curated for hepatocyte biomarkers (fabp10a, and apoa2). Overall, 8.63 % (2390/27698) genes were significantly differentially expressed. Results from untargeted analysis revealed 22 distinct clusters that were manually annotated to specific tissues using a weight-of-evidence approach. The clusters with the highest number of significant differentially expressed genes (DEGs) were digestive organs, muscle, and otolith. Additionally, we assessed the distribution of pathway-specific genes known to be involved in PFOS toxicity: the PPAR pathway, β-oxidation of fatty acids, the Nfe2l2 pathway, and epigenetic modifications by DNA methylation, across clusters and identified the blood-related tissue to be the most sensitive. The curated hepatocyte cluster showed 220 significant DEGs and was enriched for the Notch signaling pathway. These findings provide insights into both established and novel sensitive target tissues and molecular mechanisms of developmental toxicity of PFOS.

Keywords: PFAS; PFOS; Single-cell RNA sequencing; Transcriptomics; Zebrafish.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References

    1. Alhamdoosh M, Ng M, Wilson NJ, Sheridan JM, Huynh H, Wilson MJ, Ritchie ME, 2017. Combining multiple tools outperforms individual methods in gene set enrichment analyses. Bioinformatics 33, 414–424. - PMC - PubMed
    1. Altbürger C, Rath M, Armbruster D, Driever W, 2024. Neurog1 and Olig2 integrate patterning and neurogenesis signals in development of zebrafish dopaminergic and glutamatergic dual transmitter neurons. Developmental Biology 505, 85–98. - PubMed
    1. Aluru N, 2017. Epigenetic effects of environmental chemicals: insights from zebrafish. Current Opinion in Toxicology 6, 26–33. - PMC - PubMed
    1. Andrews NC, Erdjument-Bromage H, Davidson MB, Tempst P, Orkin SH, 1993. Erythroid transcription factor NF-E2 is a haematopoietic-specific basic–leucine zipper protein. Nature 362, 722–728. - PubMed
    1. Ankley GT, Kuehl DW, Kahl MD, Jensen KM, Linnum A, Leino RL, Villeneuve DA, 2005. Reproductive and developmental toxicity and bioconcentration of perfluorooctanesulfonate in a partial life-cycle test with the fathead minnow (Pimephales promelas). Environmental Toxicology and Chemistry 24, 2316–2324. - PubMed

LinkOut - more resources