Multistage hematopoietic stem cell regulation in the mouse: A combined biological and mathematical approach

Summary: We have reconciled steady-state and stress hematopoiesis in a single mathematical model based on murine in vivo experiments and with a focus on hematopoietic stem and progenitor cells. A phenylhydrazine stress was first applied to mice. A reduced cell number in each progenitor compartment w...

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Autores principales: Céline Bonnet, Panhong Gou, Simon Girel, Vincent Bansaye, Catherine Lacout, Karine Bailly, Marie-Hélène Schlagetter, Evelyne Lauret, Sylvie Méléard, Stéphane Giraudier
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Publicado: Elsevier 2021
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Acceso en línea:https://doaj.org/article/51509df1070a4d4585faa5eea2a5d7f2
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spelling oai:doaj.org-article:51509df1070a4d4585faa5eea2a5d7f22021-11-24T04:33:00ZMultistage hematopoietic stem cell regulation in the mouse: A combined biological and mathematical approach2589-004210.1016/j.isci.2021.103399https://doaj.org/article/51509df1070a4d4585faa5eea2a5d7f22021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221013705https://doaj.org/toc/2589-0042Summary: We have reconciled steady-state and stress hematopoiesis in a single mathematical model based on murine in vivo experiments and with a focus on hematopoietic stem and progenitor cells. A phenylhydrazine stress was first applied to mice. A reduced cell number in each progenitor compartment was evidenced during the next 7 days through a drastic level of differentiation without proliferation, followed by a huge proliferative response in all compartments including long-term hematopoietic stem cells, before a return to normal levels. Data analysis led to the addition to the 6-compartment model, of time-dependent regulation that depended indirectly on the compartment sizes. The resulting model was finely calibrated using a stochastic optimization algorithm and could reproduce biological data in silico when applied to different stress conditions (bleeding, chemotherapy, HSC depletion). In conclusion, our multi-step and time-dependent model of immature hematopoiesis provides new avenues to a better understanding of both normal and pathological hematopoiesis.Céline BonnetPanhong GouSimon GirelVincent BansayeCatherine LacoutKarine BaillyMarie-Hélène SchlagetterEvelyne LauretSylvie MéléardStéphane GiraudierElsevierarticleCell biologyStem cells researchIn silico biologyScienceQENiScience, Vol 24, Iss 12, Pp 103399- (2021)
institution DOAJ
collection DOAJ
language EN
topic Cell biology
Stem cells research
In silico biology
Science
Q
spellingShingle Cell biology
Stem cells research
In silico biology
Science
Q
Céline Bonnet
Panhong Gou
Simon Girel
Vincent Bansaye
Catherine Lacout
Karine Bailly
Marie-Hélène Schlagetter
Evelyne Lauret
Sylvie Méléard
Stéphane Giraudier
Multistage hematopoietic stem cell regulation in the mouse: A combined biological and mathematical approach
description Summary: We have reconciled steady-state and stress hematopoiesis in a single mathematical model based on murine in vivo experiments and with a focus on hematopoietic stem and progenitor cells. A phenylhydrazine stress was first applied to mice. A reduced cell number in each progenitor compartment was evidenced during the next 7 days through a drastic level of differentiation without proliferation, followed by a huge proliferative response in all compartments including long-term hematopoietic stem cells, before a return to normal levels. Data analysis led to the addition to the 6-compartment model, of time-dependent regulation that depended indirectly on the compartment sizes. The resulting model was finely calibrated using a stochastic optimization algorithm and could reproduce biological data in silico when applied to different stress conditions (bleeding, chemotherapy, HSC depletion). In conclusion, our multi-step and time-dependent model of immature hematopoiesis provides new avenues to a better understanding of both normal and pathological hematopoiesis.
format article
author Céline Bonnet
Panhong Gou
Simon Girel
Vincent Bansaye
Catherine Lacout
Karine Bailly
Marie-Hélène Schlagetter
Evelyne Lauret
Sylvie Méléard
Stéphane Giraudier
author_facet Céline Bonnet
Panhong Gou
Simon Girel
Vincent Bansaye
Catherine Lacout
Karine Bailly
Marie-Hélène Schlagetter
Evelyne Lauret
Sylvie Méléard
Stéphane Giraudier
author_sort Céline Bonnet
title Multistage hematopoietic stem cell regulation in the mouse: A combined biological and mathematical approach
title_short Multistage hematopoietic stem cell regulation in the mouse: A combined biological and mathematical approach
title_full Multistage hematopoietic stem cell regulation in the mouse: A combined biological and mathematical approach
title_fullStr Multistage hematopoietic stem cell regulation in the mouse: A combined biological and mathematical approach
title_full_unstemmed Multistage hematopoietic stem cell regulation in the mouse: A combined biological and mathematical approach
title_sort multistage hematopoietic stem cell regulation in the mouse: a combined biological and mathematical approach
publisher Elsevier
publishDate 2021
url https://doaj.org/article/51509df1070a4d4585faa5eea2a5d7f2
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