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Boolean modeling reveals that cyclic attractors in macrophage polarization serve as reservoirs of states to balance external perturbations from the tumor microenvironment.
de León, Ugo Avila-Ponce; Vázquez-Jiménez, Aarón; Matadamas-Guzmán, Meztli; Resendis-Antonio, Osbaldo.
  • de León UA; Programa de Doctorado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.
  • Vázquez-Jiménez A; Human Systems Biology Laboratory, Instituto Nacional de Medicina Genómica (INMEGEN), Ciudad de México, Mexico.
  • Matadamas-Guzmán M; Human Systems Biology Laboratory, Instituto Nacional de Medicina Genómica (INMEGEN), Ciudad de México, Mexico.
  • Resendis-Antonio O; Human Systems Biology Laboratory, Instituto Nacional de Medicina Genómica (INMEGEN), Ciudad de México, Mexico.
Front Immunol ; 13: 1012730, 2022.
Article in English | MEDLINE | ID: covidwho-2215266
ABSTRACT
Cyclic attractors generated from Boolean models may explain the adaptability of a cell in response to a dynamical complex tumor microenvironment. In contrast to this idea, we postulate that cyclic attractors in certain cases could be a systemic mechanism to face the perturbations coming from the environment. To justify our conjecture, we present a dynamic analysis of a highly curated transcriptional regulatory network of macrophages constrained into a cancer microenvironment. We observed that when M1-associated transcription factors (STAT1 or NF-κB) are perturbed and the microenvironment balances to a hyper-inflammation condition, cycle attractors activate genes whose signals counteract this effect implicated in tissue damage. The same behavior happens when the M2-associated transcription factors are disturbed (STAT3 or STAT6); cycle attractors will prevent a hyper-regulation scenario implicated in providing a suitable environment for tumor growth. Therefore, here we propose that cyclic macrophage phenotypes can serve as a reservoir for balancing the phenotypes when a specific phenotype-based transcription factor is perturbed in the regulatory network of macrophages. We consider that cyclic attractors should not be simply ignored, but it is necessary to carefully evaluate their biological importance. In this work, we suggest one conjecture the cyclic attractors can serve as a reservoir to balance the inflammatory/regulatory response of the network under external perturbations.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Algorithms / Tumor Microenvironment Type of study: Experimental Studies Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.1012730

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Algorithms / Tumor Microenvironment Type of study: Experimental Studies Language: English Journal: Front Immunol Year: 2022 Document Type: Article Affiliation country: Fimmu.2022.1012730