An ancestral molecular response to nanomaterial particulates
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Date
Authors
Del Giudice, G.
Serra, A.
Saarimaki, L.A.
Kotsis, K.
Rouse, I.
Colibaba, S.A.
Jagiello, K.
Mikolajczyk, A.
Fratello, M.
Papadiamantis, A.G.
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Research
Abstract
The varied transcriptomic response to nanoparticles has hampered
the understanding of the mechanism of action. Here, by performing a
meta-analysis of a large collection of transcriptomics data from various
engineered nanoparticle exposure studies, we identify common patterns of
gene regulation that impact the transcriptomic response. Analysis identifies
deregulation of immune functions as a prominent response across different
exposure studies. Looking at the promoter regions of these genes, a set of
binding sites for zinc finger transcription factors C2H2, involved in cell stress
responses, protein misfolding and chromatin remodelling and
immunomodulation,
is identified. The model can be used to explain the outcomes of
mechanism of action and is observed across a range of species indicating
this is a conserved part of the innate immune system.
Description
DATA AVAILABILITY : The pre-processed version of the transcriptomic datasets included in
the discovery datasets, that is, ENM exposures of human and mouse
samples, have been previously deposited at https://zenodo.org/
record/3949890#.YlPUri0RqH0. The original datasets can be accessed
at Array Express (https://www.ebi.ac.uk/biostudies/arrayexpress) with
the entry code EMTAB6396 and at GEO (https://www.ncbi.nlm.nih.
gov/) under accession numbers GSE103101, GSE112780, GSE113088,
GSE117056, GSE122197, GSE127773, GSE146708, GSE148705, GSE157266,
GSE16727, GSE17676, GSE19487, GSE20692, GSE29042, GSE35193,
GSE39330, GSE41041, GSE42066, GSE42067, GSE42068, GSE43515,
GSE45322, GSE45598, GSE4567, GSE46998, GSE46999, GSE50176,
GSE51186, GSE51417, GSE51421, GSE51636, GSE53700, GSE55286,
GSE55349, GSE56324, GSE56325, GSE60797, GSE60798, GSE60799,
GSE60800, GSE61366, GSE62253, GSE62769, GSE63552, GSE63806,
GSE68036, GSE75429, GSE79766, GSE81564, GSE81565, GSE81566,
GSE81567, GSE81568, GSE81569, GSE82062, GSE84982, GSE85711,
GSE88786, GSE92563, GSE92900, GSE92987, GSE96720, GSE98236
and GSE99929.
Transcriptomic datasets used for the eco-toxicological analysis
are freely available at GEO under accession numbers GSE80461,
GSE32521, GSE70509, GSE73427, GSE77148, GSE41333 and GSE47662.
Transcriptomic datasets of small molecule exposure (Open-TG GATEs)
have been downloaded from https://dbarchive.biosciencedbc.jp/en/
open-tggates/download.html in November 2020. Functional data
were downloaded from https://www.gsea-msigdb.org/gsea/msigdb/
version 7.2.
All the other relevant data and data supporting the findings of this study have been deposited in the online Zenodo repository
(https://doi.org/10.5281/zenodo.7674574).
CODE AVAILABILITY : All the relevant and custom code supporting the findings of this study has been deposited in the online Zenodo repository (https://DOI. org/10.5281/zenodo.7674574) and on Github at https://github.com/ fhaive/metanalysis_toxicogenomic_data.
CODE AVAILABILITY : All the relevant and custom code supporting the findings of this study has been deposited in the online Zenodo repository (https://DOI. org/10.5281/zenodo.7674574) and on Github at https://github.com/ fhaive/metanalysis_toxicogenomic_data.
Keywords
Transcriptomic, Nanoparticles, Mechanism, Innate immune system, SDG-03: Good health and well-being
Sustainable Development Goals
SDG-03:Good heatlh and well-being
Citation
Del Giudice, G., Serra, A., Saarimaki, L.A. et al. 2023, 'An ancestral molecular response to nanomaterial particulates', Nature Nanotechnology, vol. 18, pp. 957-966.
https://DOI.org/10.1038/s41565-023-01393-4.