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Integrated single cell analysis shows chronic alcohol drinking disrupts monocyte differentiation in the bone marrow
Chronic heavy alcohol drinking (CHD) rewires monocytes and macrophages toward heightened inflammatory states with compromised antimicrobial defenses that persist after 1-month abstinence. To determine whether these changes are mediated through alterations in the bone marrow niche, we profiled monocy...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10545484/ https://www.ncbi.nlm.nih.gov/pubmed/37657446 http://dx.doi.org/10.1016/j.stemcr.2023.08.001 |
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author | Lewis, Sloan A. Doratt, Brianna M. Qiao, Qi Blanton, Madison Grant, Kathleen A. Messaoudi, Ilhem |
author_facet | Lewis, Sloan A. Doratt, Brianna M. Qiao, Qi Blanton, Madison Grant, Kathleen A. Messaoudi, Ilhem |
author_sort | Lewis, Sloan A. |
collection | PubMed |
description | Chronic heavy alcohol drinking (CHD) rewires monocytes and macrophages toward heightened inflammatory states with compromised antimicrobial defenses that persist after 1-month abstinence. To determine whether these changes are mediated through alterations in the bone marrow niche, we profiled monocytes and hematopoietic stem cell progenitors (HSCPs) from CHD rhesus macaques using a combination of functional assays and single cell genomics. CHD resulted in transcriptional profiles consistent with increased activation and inflammation within bone marrow resident monocytes and macrophages. Furthermore, CHD resulted in transcriptional signatures associated with increased oxidative and cellular stress in HSCP. Differentiation of HSCP in vitro revealed skewing toward monocytes expressing “neutrophil-like” markers with greater inflammatory responses to bacterial agonists. Further analyses of HSCPs showed broad epigenetic changes that were in line with exacerbated inflammatory responses within monocytes and their progenitors. In summary, CHD alters HSCPs in the bone marrow leading to the production of monocytes poised to generate dysregulated hyper-inflammatory responses. |
format | Online Article Text |
id | pubmed-10545484 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-105454842023-10-04 Integrated single cell analysis shows chronic alcohol drinking disrupts monocyte differentiation in the bone marrow Lewis, Sloan A. Doratt, Brianna M. Qiao, Qi Blanton, Madison Grant, Kathleen A. Messaoudi, Ilhem Stem Cell Reports Article Chronic heavy alcohol drinking (CHD) rewires monocytes and macrophages toward heightened inflammatory states with compromised antimicrobial defenses that persist after 1-month abstinence. To determine whether these changes are mediated through alterations in the bone marrow niche, we profiled monocytes and hematopoietic stem cell progenitors (HSCPs) from CHD rhesus macaques using a combination of functional assays and single cell genomics. CHD resulted in transcriptional profiles consistent with increased activation and inflammation within bone marrow resident monocytes and macrophages. Furthermore, CHD resulted in transcriptional signatures associated with increased oxidative and cellular stress in HSCP. Differentiation of HSCP in vitro revealed skewing toward monocytes expressing “neutrophil-like” markers with greater inflammatory responses to bacterial agonists. Further analyses of HSCPs showed broad epigenetic changes that were in line with exacerbated inflammatory responses within monocytes and their progenitors. In summary, CHD alters HSCPs in the bone marrow leading to the production of monocytes poised to generate dysregulated hyper-inflammatory responses. Elsevier 2023-08-31 /pmc/articles/PMC10545484/ /pubmed/37657446 http://dx.doi.org/10.1016/j.stemcr.2023.08.001 Text en © 2023 The Author(s) 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/). |
spellingShingle | Article Lewis, Sloan A. Doratt, Brianna M. Qiao, Qi Blanton, Madison Grant, Kathleen A. Messaoudi, Ilhem Integrated single cell analysis shows chronic alcohol drinking disrupts monocyte differentiation in the bone marrow |
title | Integrated single cell analysis shows chronic alcohol drinking disrupts monocyte differentiation in the bone marrow |
title_full | Integrated single cell analysis shows chronic alcohol drinking disrupts monocyte differentiation in the bone marrow |
title_fullStr | Integrated single cell analysis shows chronic alcohol drinking disrupts monocyte differentiation in the bone marrow |
title_full_unstemmed | Integrated single cell analysis shows chronic alcohol drinking disrupts monocyte differentiation in the bone marrow |
title_short | Integrated single cell analysis shows chronic alcohol drinking disrupts monocyte differentiation in the bone marrow |
title_sort | integrated single cell analysis shows chronic alcohol drinking disrupts monocyte differentiation in the bone marrow |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10545484/ https://www.ncbi.nlm.nih.gov/pubmed/37657446 http://dx.doi.org/10.1016/j.stemcr.2023.08.001 |
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