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Transcriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity
Macrophages are ubiquitous custodians of tissues, which play decisive role in maintaining cellular homeostasis through regulatory immune responses. Within tissues, macrophage exhibit extremely heterogeneous population with varying functions orchestrated through regulatory response, which can be furt...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016976/ https://www.ncbi.nlm.nih.gov/pubmed/33795737 http://dx.doi.org/10.1038/s41598-021-86742-w |
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author | Mishra, Bharat Athar, Mohammad Mukhtar, M. Shahid |
author_facet | Mishra, Bharat Athar, Mohammad Mukhtar, M. Shahid |
author_sort | Mishra, Bharat |
collection | PubMed |
description | Macrophages are ubiquitous custodians of tissues, which play decisive role in maintaining cellular homeostasis through regulatory immune responses. Within tissues, macrophage exhibit extremely heterogeneous population with varying functions orchestrated through regulatory response, which can be further exacerbated in diverse genetic backgrounds. Gene regulatory networks (GRNs) offer comprehensive understanding of cellular regulatory behavior by unfolding the transcription factors (TFs) and regulated target genes. RNA-Seq coupled with ATAC-Seq has revolutionized the regulome landscape influenced by gene expression modeling. Here, we employ an integrative multi-omics systems biology-based analysis and generated GRNs derived from the unstimulated bone marrow-derived macrophages of five inbred genetically defined murine strains, which are reported to be linked with most of the population-wide human genetic variants. Our probabilistic modeling of a basal hemostasis pan regulatory repertoire in diverse macrophages discovered 96 TFs targeting 6279 genes representing 468,291 interactions across five inbred murine strains. Subsequently, we identify core and distinctive GRN sub-networks in unstimulated macrophages to describe the system-wide conservation and dissimilarities, respectively across five murine strains. Our study concludes that discrepancies in unstimulated macrophage-specific regulatory networks not only drives the basal functional plasticity within genetic backgrounds, additionally aid in understanding the complexity of racial disparity among the human population during stress. |
format | Online Article Text |
id | pubmed-8016976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80169762021-04-07 Transcriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity Mishra, Bharat Athar, Mohammad Mukhtar, M. Shahid Sci Rep Article Macrophages are ubiquitous custodians of tissues, which play decisive role in maintaining cellular homeostasis through regulatory immune responses. Within tissues, macrophage exhibit extremely heterogeneous population with varying functions orchestrated through regulatory response, which can be further exacerbated in diverse genetic backgrounds. Gene regulatory networks (GRNs) offer comprehensive understanding of cellular regulatory behavior by unfolding the transcription factors (TFs) and regulated target genes. RNA-Seq coupled with ATAC-Seq has revolutionized the regulome landscape influenced by gene expression modeling. Here, we employ an integrative multi-omics systems biology-based analysis and generated GRNs derived from the unstimulated bone marrow-derived macrophages of five inbred genetically defined murine strains, which are reported to be linked with most of the population-wide human genetic variants. Our probabilistic modeling of a basal hemostasis pan regulatory repertoire in diverse macrophages discovered 96 TFs targeting 6279 genes representing 468,291 interactions across five inbred murine strains. Subsequently, we identify core and distinctive GRN sub-networks in unstimulated macrophages to describe the system-wide conservation and dissimilarities, respectively across five murine strains. Our study concludes that discrepancies in unstimulated macrophage-specific regulatory networks not only drives the basal functional plasticity within genetic backgrounds, additionally aid in understanding the complexity of racial disparity among the human population during stress. Nature Publishing Group UK 2021-04-01 /pmc/articles/PMC8016976/ /pubmed/33795737 http://dx.doi.org/10.1038/s41598-021-86742-w Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Mishra, Bharat Athar, Mohammad Mukhtar, M. Shahid Transcriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity |
title | Transcriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity |
title_full | Transcriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity |
title_fullStr | Transcriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity |
title_full_unstemmed | Transcriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity |
title_short | Transcriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity |
title_sort | transcriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016976/ https://www.ncbi.nlm.nih.gov/pubmed/33795737 http://dx.doi.org/10.1038/s41598-021-86742-w |
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