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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2021
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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) |
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Cell biology Stem cells research In silico biology Science Q |
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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 |
work_keys_str_mv |
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