Transcriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity

Abstract 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 ca...

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Autores principales:	Bharat Mishra, Mohammad Athar, M. Shahid Mukhtar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e70ff61fcd6647f7b300a9fe0725a619
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spelling	oai:doaj.org-article:e70ff61fcd6647f7b300a9fe0725a6192021-12-02T14:23:13ZTranscriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity10.1038/s41598-021-86742-w2045-2322https://doaj.org/article/e70ff61fcd6647f7b300a9fe0725a6192021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86742-whttps://doaj.org/toc/2045-2322Abstract 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.Bharat MishraMohammad AtharM. Shahid MukhtarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bharat Mishra Mohammad Athar M. Shahid Mukhtar Transcriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity
description	Abstract 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	article
author	Bharat Mishra Mohammad Athar M. Shahid Mukhtar
author_facet	Bharat Mishra Mohammad Athar M. Shahid Mukhtar
author_sort	Bharat Mishra
title	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_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_sort	transcriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e70ff61fcd6647f7b300a9fe0725a619
work_keys_str_mv	AT bharatmishra transcriptionalcircuitryatlasofgeneticdiverseunstimulatedmurineandhumanmacrophagesdefinedisparityinpopulationwideinnateimmunity AT mohammadathar transcriptionalcircuitryatlasofgeneticdiverseunstimulatedmurineandhumanmacrophagesdefinedisparityinpopulationwideinnateimmunity AT mshahidmukhtar transcriptionalcircuitryatlasofgeneticdiverseunstimulatedmurineandhumanmacrophagesdefinedisparityinpopulationwideinnateimmunity
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Transcriptional circuitry atlas of genetic diverse unstimulated murine and human macrophages define disparity in population-wide innate immunity

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