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Authors
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Bach, E. ; Zerjatke, T. ; Herklotz, M. ; Scherf, N. ; Niederwieser, D. ; Roeder, I. ; Pompe, T. ; Cross, M. ; Glauche, I.
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Title
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Elucidating functional heterogeneity in hematopoietic progenitor cells: a combined experimental and modeling approach
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Date
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28.05.2014
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Number
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38706
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Abstract
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A detailed understanding of the mechanisms maintaining the hierarchical balance of cell types in haematopoiesis will be important for the therapeutic manipulation of normal and leukaemic cells. Mathematical modelling is expected to make an important contribution to this area, but the iterative development of increasingly accurate models will rely on repeated validation using experimental data of sufficient resolution to distinguish between alternative model scenarios. The multipotent hematopoietic progenitor FDCP-Mix cells maintain a hierarchy from self-renewal to post-mitotic differentiation in vitro and are accessible to detailed analysis. Here, we report the development of a combined mathematical modelling and experimental approach to study the principles underlying heterogeneity in FDCP-Mix cultures. We adapt a single-cell based model of haematopoiesis to the conditions of cell culture and describe an association between proliferative history and phenotype of FDCP-Mix cells. While data derived from population studies are incapable of distinguishing between three mechanistically different model scenarios, statistical analysis of single cell tracking data provides a resolution sufficient to select one of them. This scenario favours differences between granulocytic and monocytic lineage with respect to their proliferative behaviour and death rates as a mechanistic explanation for the observed heterogeneity. Our results demonstrate the power of a combined experimental/modelling approach in which single cell fate analysis is the key to revealing regulatory principles at the cellular level.
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Publisher
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Experimental Hematology
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Wikidata
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Citation
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Experimental Hematology 42 (2014) 826-837.e17
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DOI
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https://doi.org/10.1016/j.exphem.2014.05.011
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Tags
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haematopoietic stem cells self-renewal time-lapse video microscopy single cell tracking mathematical modelling
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