Multi-scale modeling of GMP differentiation based on single-cell genealogies

The FEBS Journal
Carsten MarrFabian J Theis

Abstract

Hematopoiesis is often pictured as a hierarchy of branching decisions, giving rise to all mature blood cell types from stepwise differentiation of a single cell, the hematopoietic stem cell. Various aspects of this process have been modeled using various experimental and theoretical techniques on different scales. Here we integrate the more common population-based approach with a single-cell resolved molecular differentiation model to study the possibility of inferring mechanistic knowledge of the differentiation process. We focus on a sub-module of hematopoiesis: differentiation of granulocyte-monocyte progenitors (GMPs) to granulocytes or monocytes. Within a branching process model, we infer the differentiation probability of GMPs from the experimentally quantified heterogeneity of colony assays under permissive conditions where both granulocytes and monocytes can emerge. We compare the predictions with the differentiation probability in genealogies determined from single-cell time-lapse microscopy. In contrast to the branching process model, we found that the differentiation probability as determined by differentiation marker onset increases with the generation of the cell within the genealogy. To study this feature from a m...Continue Reading

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Related Concepts

Colony-Forming Units, Hematopoietic
Murine
Granulocyte Count
Cell Differentiation Process
Cell Lineage
Microscopy
Psychological Techniques
Monocytes as Percentage of Blood Leukocytes (Lab Test)
Granulocyte
Bayesian Prediction

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