Computational Modeling of Stem and Progenitor Cell Kinetics Identifies Plausible Hematopoietic Lineage Hierarchies

Overview

Journal iScience

Publisher Cell Press

Date 2021 Mar 5

PMID 33665548

Citations 3

Authors

Lisa Bast

Michele C Buck

Judith S Hecker

Robert A J Oostendorp

Katharina S Gotze

Carsten Marr

Affiliations

Soon will be listed here.

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 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.

Citing Articles

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