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Single-Cell Multi-Omics Profiling of Immune Cells Isolated from Atherosclerotic Plaques in Male ApoE Knockout Mice Exposed to Arsenic.

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Title: Single-Cell Multi-Omics Profiling of Immune Cells Isolated from Atherosclerotic Plaques in Male ApoE Knockout Mice Exposed to Arsenic.
Authors: Makhani, Kiran1,2, Xiuhui Yang3,4,5,6, Dierick, France2, Subramaniam, Nivetha1,2, Gagnon, Natascha2, Ebrahimian, Talin2, Lehoux, Stephanie2,4, Hao Wu5, Jun Ding1,3,4,6,7,8,9 jun.ding@mcgill.ca, Mann, Koren K.1,2,10 koren.mann@mcgill.ca
Source: Environmental Health Perspectives. Jan2025, Vol. 133 Issue 1, p017007-1-017007-18. 18p.
Subject Terms: *Environmental exposure, *Animal experimentation, *Water pollution, *Arsenic, Atherosclerosis risk factors, Biological models, T cells, Research funding, Multiomics, Epigenomics, Transcription factors, Immune system, Atherosclerosis, Dietary fats, Descriptive statistics, Mice, Messenger RNA, Pathological anatomy, Apolipoproteins, Chromosomes
Abstract: BACKGROUND: Millions worldwide are exposed to elevated levels of arsenic that significantly increase their risk of developing atherosclerosis, a pathology primarily driven by immune cells. While the impact of arsenic on immune cell populations in atherosclerotic plaques has been broadly characterized, cellular heterogeneity is a substantial barrier to in-depth examinations of the cellular dynamics for varying immune cell populations. OBJECTIVES: This study aimed to conduct single-cell multi-omics profiling of atherosclerotic plaques in apolipoprotein E knockout (ApoE–/– ) mice to elucidate transcriptomic and epigenetic changes in immune cells induced by arsenic exposure. METHODS: The ApoE–/– mice were fed a high-fat diet and were exposed to either 200 ppb arsenic in drinking water or a tap water control, and single-cell multi-omics profiling was performed on atherosclerotic plaque-resident immune cells. Transcriptomic and epigenetic changes in immune cells were analyzed within the same cell to understand the effects of arsenic exposure. RESULTS: Our data revealed that the transcriptional profile of macrophages from arsenic-exposed mice were significantly different from that of control mice and that differences were subtype specific and associated with cell–cell interaction and cell fates. Additionally, our data suggest that differences in arsenic-mediated changes in chromosome accessibility in arsenic-exposed mice were statistically more likely to be due to factors other than random variation compared to their effects on the transcriptome, revealing markers of arsenic exposure and potential targets for intervention. DISCUSSION: These findings in mice provide insights into how arsenic exposure impacts immune cell types in atherosclerosis, highlighting the importance of considering cellular heterogeneity in studying such effects. The identification of subtype-specific differences and potential intervention targets underscores the significance of understanding the molecular mechanisms underlying arsenic-induced atherosclerosis. Further research is warranted to validate these findings and explore therapeutic interventions targeting immune cell dysfunction in arsenic-exposed individuals. [ABSTRACT FROM AUTHOR]
Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Single-Cell Multi-Omics Profiling of Immune Cells Isolated from Atherosclerotic Plaques in Male ApoE Knockout Mice Exposed to Arsenic.
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  Data: <searchLink fieldCode="AR" term="%22Makhani%2C+Kiran%22">Makhani, Kiran</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Xiuhui+Yang%22">Xiuhui Yang</searchLink><relatesTo>3,4,5,6</relatesTo><br /><searchLink fieldCode="AR" term="%22Dierick%2C+France%22">Dierick, France</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Subramaniam%2C+Nivetha%22">Subramaniam, Nivetha</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Gagnon%2C+Natascha%22">Gagnon, Natascha</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Ebrahimian%2C+Talin%22">Ebrahimian, Talin</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Lehoux%2C+Stephanie%22">Lehoux, Stephanie</searchLink><relatesTo>2,4</relatesTo><br /><searchLink fieldCode="AR" term="%22Hao+Wu%22">Hao Wu</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Jun+Ding%22">Jun Ding</searchLink><relatesTo>1,3,4,6,7,8,9</relatesTo><i> jun.ding@mcgill.ca</i><br /><searchLink fieldCode="AR" term="%22Mann%2C+Koren+K%2E%22">Mann, Koren K.</searchLink><relatesTo>1,2,10</relatesTo><i> koren.mann@mcgill.ca</i>
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  Data: <searchLink fieldCode="JN" term="%22Environmental+Health+Perspectives%22">Environmental Health Perspectives</searchLink>. Jan2025, Vol. 133 Issue 1, p017007-1-017007-18. 18p.
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  Data: *<searchLink fieldCode="DE" term="%22Environmental+exposure%22">Environmental exposure</searchLink><br />*<searchLink fieldCode="DE" term="%22Animal+experimentation%22">Animal experimentation</searchLink><br />*<searchLink fieldCode="DE" term="%22Water+pollution%22">Water pollution</searchLink><br />*<searchLink fieldCode="DE" term="%22Arsenic%22">Arsenic</searchLink><br /><searchLink fieldCode="DE" term="%22Atherosclerosis+risk+factors%22">Atherosclerosis risk factors</searchLink><br /><searchLink fieldCode="DE" term="%22Biological+models%22">Biological models</searchLink><br /><searchLink fieldCode="DE" term="%22T+cells%22">T cells</searchLink><br /><searchLink fieldCode="DE" term="%22Research+funding%22">Research funding</searchLink><br /><searchLink fieldCode="DE" term="%22Multiomics%22">Multiomics</searchLink><br /><searchLink fieldCode="DE" term="%22Epigenomics%22">Epigenomics</searchLink><br /><searchLink fieldCode="DE" term="%22Transcription+factors%22">Transcription factors</searchLink><br /><searchLink fieldCode="DE" term="%22Immune+system%22">Immune system</searchLink><br /><searchLink fieldCode="DE" term="%22Atherosclerosis%22">Atherosclerosis</searchLink><br /><searchLink fieldCode="DE" term="%22Dietary+fats%22">Dietary fats</searchLink><br /><searchLink fieldCode="DE" term="%22Descriptive+statistics%22">Descriptive statistics</searchLink><br /><searchLink fieldCode="DE" term="%22Mice%22">Mice</searchLink><br /><searchLink fieldCode="DE" term="%22Messenger+RNA%22">Messenger RNA</searchLink><br /><searchLink fieldCode="DE" term="%22Pathological+anatomy%22">Pathological anatomy</searchLink><br /><searchLink fieldCode="DE" term="%22Apolipoproteins%22">Apolipoproteins</searchLink><br /><searchLink fieldCode="DE" term="%22Chromosomes%22">Chromosomes</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: BACKGROUND: Millions worldwide are exposed to elevated levels of arsenic that significantly increase their risk of developing atherosclerosis, a pathology primarily driven by immune cells. While the impact of arsenic on immune cell populations in atherosclerotic plaques has been broadly characterized, cellular heterogeneity is a substantial barrier to in-depth examinations of the cellular dynamics for varying immune cell populations. OBJECTIVES: This study aimed to conduct single-cell multi-omics profiling of atherosclerotic plaques in apolipoprotein E knockout (ApoE–/– ) mice to elucidate transcriptomic and epigenetic changes in immune cells induced by arsenic exposure. METHODS: The ApoE–/– mice were fed a high-fat diet and were exposed to either 200 ppb arsenic in drinking water or a tap water control, and single-cell multi-omics profiling was performed on atherosclerotic plaque-resident immune cells. Transcriptomic and epigenetic changes in immune cells were analyzed within the same cell to understand the effects of arsenic exposure. RESULTS: Our data revealed that the transcriptional profile of macrophages from arsenic-exposed mice were significantly different from that of control mice and that differences were subtype specific and associated with cell–cell interaction and cell fates. Additionally, our data suggest that differences in arsenic-mediated changes in chromosome accessibility in arsenic-exposed mice were statistically more likely to be due to factors other than random variation compared to their effects on the transcriptome, revealing markers of arsenic exposure and potential targets for intervention. DISCUSSION: These findings in mice provide insights into how arsenic exposure impacts immune cell types in atherosclerosis, highlighting the importance of considering cellular heterogeneity in studying such effects. The identification of subtype-specific differences and potential intervention targets underscores the significance of understanding the molecular mechanisms underlying arsenic-induced atherosclerosis. Further research is warranted to validate these findings and explore therapeutic interventions targeting immune cell dysfunction in arsenic-exposed individuals. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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    Identifiers:
      – Type: doi
        Value: 10.1289/EHP14285
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      – Code: eng
        Text: English
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      – SubjectFull: Environmental exposure
        Type: general
      – SubjectFull: Animal experimentation
        Type: general
      – SubjectFull: Water pollution
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      – SubjectFull: Arsenic
        Type: general
      – SubjectFull: Atherosclerosis risk factors
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      – SubjectFull: Biological models
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      – SubjectFull: T cells
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      – SubjectFull: Research funding
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      – SubjectFull: Multiomics
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      – SubjectFull: Epigenomics
        Type: general
      – SubjectFull: Transcription factors
        Type: general
      – SubjectFull: Immune system
        Type: general
      – SubjectFull: Atherosclerosis
        Type: general
      – SubjectFull: Dietary fats
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      – SubjectFull: Descriptive statistics
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      – SubjectFull: Mice
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      – SubjectFull: Apolipoproteins
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      – SubjectFull: Chromosomes
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      – TitleFull: Single-Cell Multi-Omics Profiling of Immune Cells Isolated from Atherosclerotic Plaques in Male ApoE Knockout Mice Exposed to Arsenic.
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              M: 01
              Text: Jan2025
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