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Bast, L. ; Buck, M.C.* ; Hecker, J.S.* ; Oostendorp, R.A.J.* ; Götze, K.S.* ; Marr, C.

Computational modeling of stem and progenitor cell kinetics identifies plausible hematopoietic lineage hierarchies.

iScience 24:102120 (2021)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag

Classically, hematopoietic stem cell (HSC) differentiation is assumed to occur via progenitor compartments of decreasing plasticity and increasing maturity in a specific, hierarchical manner. The classical hierarchy has been challenged in the past by alternative differentiation pathways. We abstracted experimental evidence into 10 differentiation hierarchies, each comprising 7 cell type compartments. By fitting ordinary differential equation models with realistic waiting time distributions to time-resolved data of differentiating HSCs from 10 healthy human donors, we identified plausible lineage hierarchies and rejected others. We found that, for most donors, the classical model of hematopoiesis is preferred. Surprisingly, multipotent lymphoid progenitor differentiation into granulocyte-monocyte progenitors is plausible in 90% of samples. An in silico analysis confirmed that, even for strong noise, the classical model can be identified robustly. Our computational approach infers differentiation hierarchies in a personalized fashion and can be used to gain insights into kinetic alterations of diseased hematopoiesis.

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Publication type Article: Journal article
Document type Scientific Article
Keywords In Silico Biology ; Stem Cells Research ; Systems Biology; Mathematical-model; Dendritic Cells; Natural-killer; B-cells; Differentiation; Rise; Macrophages; Commitment; Map
ISSN (print) / ISBN 2589-0042
e-ISSN 2589-0042
Journal iScience
Quellenangaben Volume: 24, Issue: 2, Pages: , Article Number: 102120 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Reviewing status Peer reviewed
Grants European Research Council under the Eurpoean Unions
European Research Council (ERC) under the European Union
Joachim Herz Stiftung
Deutsche Jose Carreras Leukamie Stiftung (DJCLS)
Deutsche Forschungsgemeinschaft