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

Celine Bonnet (1, 2) , Panhong Gou (3) , Simon Girel (1, 2) , Vincent Bansaye (1, 2) , Catherine Lacout (3) , Karine Bailly (4) , Marie-Hélène Schlagetter (3) , Evelyne Lauret (4) , Sylvie Méléard (1, 2, 5) , Stéphane Giraudier (3)

1 CMAP - Centre de Mathématiques Appliquées - Ecole Polytechnique
2 IP Paris - Institut Polytechnique de Paris
3 (UMR_S1131 / U1131) - Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris]
4 IC UM3 (UMR 8104 / U1016) - Institut Cochin
5 IUF - Institut universitaire de France

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.

Mots clés: Cell biology; In silico biology; Stem cells research

Domaines: Mathématiques [math]; Sciences du Vivant [q-bio]

Celine Bonnet, Panhong Gou, Simon Girel, Vincent Bansaye, Catherine Lacout, et al.. Multistage hematopoietic stem cell regulation in the mouse: A combined biological and mathematical approach. iScience, 2021, ⟨10.1016/j.isci.2021.103399⟩. ⟨hal-03796041⟩