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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9035596 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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