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  Elucidating functional heterogeneity in hematopoietic progenitor cells: A combined experimental and modeling approach

Bach, E., Zerjatke, T., Herklotz, M., Scherf, N., Niederwieser, D., Roeder, I., et al. (2014). Elucidating functional heterogeneity in hematopoietic progenitor cells: A combined experimental and modeling approach. Experimental Hematology, 42(9), 826-837.e17. doi:10.1016/j.exphem.2014.05.011.

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 Creators:
Bach, Enrica1, Author
Zerjatke, Thomas1, Author
Herklotz, Manuela1, Author
Scherf, Nico1, Author              
Niederwieser, Dietger1, Author
Roeder, Ingo1, Author
Pompe, Tilo1, Author
Cross, Michael1, Author
Glauche, Ingmar1, Author
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1External Organizations, ou_persistent22              

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 Abstract: A detailed understanding of the mechanisms maintaining the hierarchical balance of cell types in hematopoiesis will be important for the therapeutic manipulation of normal and leukemic cells. Mathematical modeling 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 modeling and experimental approach to study the principles underlying heterogeneity in FDCP-Mix cultures. We adapt a single-cell based model of hematopoiesis 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 favors differences between granulocytic and monocytic lineage with respect to their proliferative behavior and death rates as a mechanistic explanation for the observed heterogeneity. Our results demonstrate the power of a combined experimental/modeling approach in which single cell fate analysis is the key to revealing regulatory principles at the cellular level.

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Language(s): eng - English
 Dates: 2014-04-072013-12-022014-05-192014-05-272014-09
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.exphem.2014.05.011
PMID: 24878352
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Title: Experimental Hematology
  Other : Exp. Hematol.
Source Genre: Journal
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Publ. Info: New York [etc.] : Elsevier
Pages: - Volume / Issue: 42 (9) Sequence Number: - Start / End Page: 826 - 837.e17 Identifier: ISSN: 0301-472X
CoNE: https://pure.mpg.de/cone/journals/resource/954925510391