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Determination of the nanoparticle- and cell-specific toxicological mechanisms in 3D liver spheroids using scRNAseq analysis

Engineered nanomaterials (ENMs) are commonly used in consumer products, allowing exposure to target organs such as the lung, liver, and skin that could lead to adverse health effects in humans. To better reflect on toxicological effects in liver cells, it is important to consider the contribution of...

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Autores principales: Li, Jiulong, Diamante, Graciel, Ahn, In Sook, Wijaya, Darren, Wang, Xiang, Chang, Chong Hyun, Ha, Sung-min, Immadisetty, Kavya, Meng, Huan, Nel, André, Yang, Xia, Xia, Tian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10004129/
https://www.ncbi.nlm.nih.gov/pubmed/36911538
http://dx.doi.org/10.1016/j.nantod.2022.101652
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author Li, Jiulong
Diamante, Graciel
Ahn, In Sook
Wijaya, Darren
Wang, Xiang
Chang, Chong Hyun
Ha, Sung-min
Immadisetty, Kavya
Meng, Huan
Nel, André
Yang, Xia
Xia, Tian
author_facet Li, Jiulong
Diamante, Graciel
Ahn, In Sook
Wijaya, Darren
Wang, Xiang
Chang, Chong Hyun
Ha, Sung-min
Immadisetty, Kavya
Meng, Huan
Nel, André
Yang, Xia
Xia, Tian
author_sort Li, Jiulong
collection PubMed
description Engineered nanomaterials (ENMs) are commonly used in consumer products, allowing exposure to target organs such as the lung, liver, and skin that could lead to adverse health effects in humans. To better reflect on toxicological effects in liver cells, it is important to consider the contribution of hepatocyte morphology, function, and intercellular interactions in a dynamic 3D microenvironment. Herein, we used a 3D liver spheroid model containing hepatocyte and Kupffer cells (KCs) to study the effects of three different material compositions, namely vanadium pentoxide (V(2)O(5)), titanium dioxide (TiO(2)), or graphene oxide (GO). Additionally, we used single-cell RNA sequencing (scRNAseq) to determine the nanoparticle (NP) and cell-specific toxicological responses. A general finding was that hepatocytes exhibit more variation in gene expression and adaptation of signaling pathways than KCs. TNF-α production tied to the NF-κB pathway was a commonly affected pathway by all NPs while impacts on the metabolic function of hepatocytes were unique to V(2)O(5). V(2)O(5) NPs also showed the largest number of differentially expressed genes in both cell types, many of which are related to pro-inflammatory and apoptotic response pathways. There was also evidence of mitochondrial ROS generation and caspase-1 activation after GO and V(2)O(5) treatment, in association with cytokine production. All considered, this study provides insight into the impact of nanoparticles on gene responses in key liver cell types, providing us with a scRNAseq platform that can be used for high-content screening of nanomaterial impact on the liver, for use in biosafety and biomedical applications.
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spelling pubmed-100041292023-03-10 Determination of the nanoparticle- and cell-specific toxicological mechanisms in 3D liver spheroids using scRNAseq analysis Li, Jiulong Diamante, Graciel Ahn, In Sook Wijaya, Darren Wang, Xiang Chang, Chong Hyun Ha, Sung-min Immadisetty, Kavya Meng, Huan Nel, André Yang, Xia Xia, Tian Nano Today Article Engineered nanomaterials (ENMs) are commonly used in consumer products, allowing exposure to target organs such as the lung, liver, and skin that could lead to adverse health effects in humans. To better reflect on toxicological effects in liver cells, it is important to consider the contribution of hepatocyte morphology, function, and intercellular interactions in a dynamic 3D microenvironment. Herein, we used a 3D liver spheroid model containing hepatocyte and Kupffer cells (KCs) to study the effects of three different material compositions, namely vanadium pentoxide (V(2)O(5)), titanium dioxide (TiO(2)), or graphene oxide (GO). Additionally, we used single-cell RNA sequencing (scRNAseq) to determine the nanoparticle (NP) and cell-specific toxicological responses. A general finding was that hepatocytes exhibit more variation in gene expression and adaptation of signaling pathways than KCs. TNF-α production tied to the NF-κB pathway was a commonly affected pathway by all NPs while impacts on the metabolic function of hepatocytes were unique to V(2)O(5). V(2)O(5) NPs also showed the largest number of differentially expressed genes in both cell types, many of which are related to pro-inflammatory and apoptotic response pathways. There was also evidence of mitochondrial ROS generation and caspase-1 activation after GO and V(2)O(5) treatment, in association with cytokine production. All considered, this study provides insight into the impact of nanoparticles on gene responses in key liver cell types, providing us with a scRNAseq platform that can be used for high-content screening of nanomaterial impact on the liver, for use in biosafety and biomedical applications. 2022-12 2022-10-14 /pmc/articles/PMC10004129/ /pubmed/36911538 http://dx.doi.org/10.1016/j.nantod.2022.101652 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Li, Jiulong
Diamante, Graciel
Ahn, In Sook
Wijaya, Darren
Wang, Xiang
Chang, Chong Hyun
Ha, Sung-min
Immadisetty, Kavya
Meng, Huan
Nel, André
Yang, Xia
Xia, Tian
Determination of the nanoparticle- and cell-specific toxicological mechanisms in 3D liver spheroids using scRNAseq analysis
title Determination of the nanoparticle- and cell-specific toxicological mechanisms in 3D liver spheroids using scRNAseq analysis
title_full Determination of the nanoparticle- and cell-specific toxicological mechanisms in 3D liver spheroids using scRNAseq analysis
title_fullStr Determination of the nanoparticle- and cell-specific toxicological mechanisms in 3D liver spheroids using scRNAseq analysis
title_full_unstemmed Determination of the nanoparticle- and cell-specific toxicological mechanisms in 3D liver spheroids using scRNAseq analysis
title_short Determination of the nanoparticle- and cell-specific toxicological mechanisms in 3D liver spheroids using scRNAseq analysis
title_sort determination of the nanoparticle- and cell-specific toxicological mechanisms in 3d liver spheroids using scrnaseq analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10004129/
https://www.ncbi.nlm.nih.gov/pubmed/36911538
http://dx.doi.org/10.1016/j.nantod.2022.101652
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