Awakening the HSC: Dynamic Modeling of HSC Maintenance Unravels Regulation of the TP53 Pathway and Quiescence
Hematopoietic stem cells (HSCs) provide all types of blood cells during the entire life of the organism. HSCs are mainly quiescent and can eventually enter the cell cycle to differentiate. HSCs are maintained and tightly regulated in a particular environment. The stem cell niche regulates dormancy a...
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Published in | Frontiers in physiology Vol. 11; p. 848 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
31.07.2020
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Subjects | |
Online Access | Get full text |
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Summary: | Hematopoietic stem cells (HSCs) provide all types of blood cells during the entire life of the organism. HSCs are mainly quiescent and can eventually enter the cell cycle to differentiate. HSCs are maintained and tightly regulated in a particular environment. The stem cell niche regulates dormancy and awakening. Deregulations of this interplay can lead to hematopoietic failure and diseases. In this paper, we present a Boolean network model that recapitulates HSC regulation in virtue of external signals coming from the niche. This Boolean network integrates and summarizes the current knowledge of HSC regulation and is based on extensive literature research. Furthermore, dynamic simulations suggest a novel systemic regulation of TP53 in homeostasis. Thereby, our model indicates that TP53 activity is balanced depending on external stimulations, engaging a regulatory mechanism involving ROS regulators and RAS activated transcription factors. Finally, we investigated different mouse models and compared them to
in silico
knockout simulations. Here, the model could recapitulate
in vivo
observed behaviors and thus sustains our results. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors have contributed equally to this work This article was submitted to Systems Biology, a section of the journal Frontiers in Physiology Reviewed by: Nathan Weinstein, Universidad Nacional Autónoma de México, Mexico; Alfredo Rodríguez, National Institute of Pediatrics, Mexico Edited by: Zhike Zi, Max Planck Institute for Molecular Genetics, Germany |
ISSN: | 1664-042X 1664-042X |
DOI: | 10.3389/fphys.2020.00848 |