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Cyclic Attractors Are Critical for Macrophage Differentiation, Heterogeneity, and Plasticity

Adaptability, heterogeneity, and plasticity are the hallmarks of macrophages. How these complex properties emerge from the molecular interactions is an open question. Thus, in this study we propose an actualized regulatory network of cytokines, signaling pathways, and transcription factors to survey...

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Autores principales: Ordaz-Arias, Manuel Azaid, Díaz-Alvarez, Laura, Zúñiga, Joaquín, Martinez-Sánchez, Mariana Esther, Balderas-Martínez, Yalbi Itzel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035596/
https://www.ncbi.nlm.nih.gov/pubmed/35480895
http://dx.doi.org/10.3389/fmolb.2022.807228
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author Ordaz-Arias, Manuel Azaid
Díaz-Alvarez, Laura
Zúñiga, Joaquín
Martinez-Sánchez, Mariana Esther
Balderas-Martínez, Yalbi Itzel
author_facet Ordaz-Arias, Manuel Azaid
Díaz-Alvarez, Laura
Zúñiga, Joaquín
Martinez-Sánchez, Mariana Esther
Balderas-Martínez, Yalbi Itzel
author_sort Ordaz-Arias, Manuel Azaid
collection PubMed
description Adaptability, heterogeneity, and plasticity are the hallmarks of macrophages. How these complex properties emerge from the molecular interactions is an open question. Thus, in this study we propose an actualized regulatory network of cytokines, signaling pathways, and transcription factors to survey the differentiation, heterogeneity, and plasticity of macrophages. The network recovers attractors, which in regulatory networks correspond to cell types, that correspond to M0, M1, M2a, M2b, M2c, M2d, M2-like, and IL-6 producing cells, including multiple cyclic attractors that are stable to perturbations. These cyclic attractors reproduce experimental observations and show that oscillations result from the structure of the network. We also study the effect of the environment in the differentiation and plasticity of macrophages, showing that the observed heterogeneity in macrophage populations is a result of the regulatory network and its interaction with the micro-environment. The macrophage regulatory network gives a mechanistic explanation to the heterogeneity and plasticity of macrophages seen in vivo and in vitro, and offers insights into the mechanism that allows the immune system to react to a complex dynamic environment.
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spelling pubmed-90355962022-04-26 Cyclic Attractors Are Critical for Macrophage Differentiation, Heterogeneity, and Plasticity Ordaz-Arias, Manuel Azaid Díaz-Alvarez, Laura Zúñiga, Joaquín Martinez-Sánchez, Mariana Esther Balderas-Martínez, Yalbi Itzel Front Mol Biosci Molecular Biosciences Adaptability, heterogeneity, and plasticity are the hallmarks of macrophages. How these complex properties emerge from the molecular interactions is an open question. Thus, in this study we propose an actualized regulatory network of cytokines, signaling pathways, and transcription factors to survey the differentiation, heterogeneity, and plasticity of macrophages. The network recovers attractors, which in regulatory networks correspond to cell types, that correspond to M0, M1, M2a, M2b, M2c, M2d, M2-like, and IL-6 producing cells, including multiple cyclic attractors that are stable to perturbations. These cyclic attractors reproduce experimental observations and show that oscillations result from the structure of the network. We also study the effect of the environment in the differentiation and plasticity of macrophages, showing that the observed heterogeneity in macrophage populations is a result of the regulatory network and its interaction with the micro-environment. The macrophage regulatory network gives a mechanistic explanation to the heterogeneity and plasticity of macrophages seen in vivo and in vitro, and offers insights into the mechanism that allows the immune system to react to a complex dynamic environment. Frontiers Media S.A. 2022-04-11 /pmc/articles/PMC9035596/ /pubmed/35480895 http://dx.doi.org/10.3389/fmolb.2022.807228 Text en Copyright © 2022 Ordaz-Arias, Díaz-Alvarez, Zúñiga, Martinez-Sánchez and Balderas-Martínez. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Ordaz-Arias, Manuel Azaid
Díaz-Alvarez, Laura
Zúñiga, Joaquín
Martinez-Sánchez, Mariana Esther
Balderas-Martínez, Yalbi Itzel
Cyclic Attractors Are Critical for Macrophage Differentiation, Heterogeneity, and Plasticity
title Cyclic Attractors Are Critical for Macrophage Differentiation, Heterogeneity, and Plasticity
title_full Cyclic Attractors Are Critical for Macrophage Differentiation, Heterogeneity, and Plasticity
title_fullStr Cyclic Attractors Are Critical for Macrophage Differentiation, Heterogeneity, and Plasticity
title_full_unstemmed Cyclic Attractors Are Critical for Macrophage Differentiation, Heterogeneity, and Plasticity
title_short Cyclic Attractors Are Critical for Macrophage Differentiation, Heterogeneity, and Plasticity
title_sort cyclic attractors are critical for macrophage differentiation, heterogeneity, and plasticity
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035596/
https://www.ncbi.nlm.nih.gov/pubmed/35480895
http://dx.doi.org/10.3389/fmolb.2022.807228
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