Modelling of Hematopoietic Stem and Stromal Cell Crosstalk: Towards Prediction for Myelofibrosis Susceptibility
Project acronym: Modlm4MF
Topics: haematological diseases, mathematical models, imaging
Disciplinary fields: biology, physics, mathematics
Summary: Hematopoietic stem cells (HSCs) have long-term self-renewal and multipotent differentiation capacities that ensure life-long production of all types of blood cells. As with most tissues having high cellular turnover, hematopoietic tissue is sensitive to aging that results in senescence, and in increased incidence of myeloid malignancies. HSC aging mechanisms seem to be dependent on both cell-intrinsic and cell-extrinsic effects. In this project two lines of investigation will be pursued: 1) The first one will be dedicated to understand the molecular mechanism linked to aging physiology. A cross-fed modelling strategy will further support identification of network perturbations explaining the aging of HSCs and disease evolution, and provide predictions for interventions reverting such processes; 2)The second line of investigation will integrate quantitative results obtained by imaging BM ECM. This will be used to measure and quantify the density and orientation of ECM components in BM histological sections obtained from mouse models. Because of the quantitative nature of this new imaging modality, ECM properties will be easily integrated in mathematical models of HSC/BM micro-environment dynamics during aging and PMF progression. Overall, this project aims at using breakthrough quantitative imaging methods and well established biological systems to establish mathematical models of BM aging in order to better manage haematological age-related diseases: myelofibrosis and leukemia.
Project duration: 03/01/2018 – 02/28/2021
Call for application : Interdisciplinarité 2016