Modeling the architecture and dynamics of hematopoiesis

Focus Article

David Dingli, Jorge M. Pacheco

Published Online: Mar 26 2010

DOI: 10.1002/wsbm.56

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Abstract Hematopoiesis is a multistep process that results in the production of a variety of blood cells with different morphologies and diverse functions. All of these cells have their origin in hematopoietic stem cells Hematopoietic Stem Cells (HSCs) that replicate slowly to self‐renew and give rise to progeny cells that proceed along the path of differentiation. The process is complex with the cells responding to a wide variety of cytokines and growth factors. We discuss a model of hematopoiesis based on stochastic cell behavior. Multiple compartments are introduced to keep track of each cell division process and increasing differentiation. Despite its simplicity, the model is able to account for the salient features of hematopoiesis and is compatible with considerable and independent experimental data. The model is applicable to hematopoiesis across mammals and can be used to understand the dynamics of various disorders both in humans and in animal models. Copyright © 2009 John Wiley & Sons, Inc. This article is categorized under: Developmental Biology > Lineages

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Hematopoiesis has a tree‐like structure with the hematopoietic stem cells at the root of the process. Each cell division gives rise to progeny cells that can retain the properties of their parent cell (self‐renewal, probability 1 − ε) or differentiate (probability ε). As the progeny move further away from the HSC, their pluripotent ability is increasingly restricted (CMP, common myeloid progenitor; CLP, common lymphoid progenitor; BFU‐E, erythroid burst forming unit; CFU‐GM, granulocyte‐macrophage colony‐forming unit).

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Hematopoietic stem cells are divided into an active pool and a quiescent reserve. All active HSCs are equally represented in the circulation. Consequently, if the number of reticulocytes ( present in the blood scales with the mass of the adult species, then the number of active HSC (N_SC) should scale in the same way with mass. The progeny of HSC grow exponentially (r^C) leading to normal cellular output from hematopoiesis.

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The architecture and dynamics of hematopoiesis. (a) For the purpose of the model, cells divide symmetrically to give rise either to daughter cells that both differentiate (probability ε) or both self‐renew (probability 1 − ε). (b) The process linking HSC to the circulating blood is composed of many compartments that grow in size and with cells replicating at faster rates. C is the last compartment where cells are dividing. (c) Cell dynamics between adjacent compartments. On average, the size of each compartment is constant due to coupling of output from one compartment to replenish the ‘loss’ of cells from output into the next downstream compartment. Cellular output is linked to differentiation of the cells.

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