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

ABSTRACT: 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.

SUBMITTER: Bast L

PROVIDER: S-EPMC7897991 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Bast Lisa L Buck Michèle C MC Hecker Judith S JS Oostendorp Robert A J RAJ Götze Katharina S KS Marr Carsten C

iScience 20210129 2

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 ti ...[more]

PMID: 33665548

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

Publications

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

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