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Open Access Research

Stem cell biology is population biology: differentiation of hematopoietic multipotent progenitors to common lymphoid and myeloid progenitors

Marc Mangel12* and Michael B Bonsall3

Author Affiliations

1 Department of Applied Mathematics and Statistics, University of California, Santa Cruz, CA, USA

2 Department of Biology, University of Bergen, Bergen, Norway

3 Mathematical Ecology Research Group, Department of Zoology, University of Oxford and St Peter’s College, Oxford, UK

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Theoretical Biology and Medical Modelling 2013, 10:5  doi:10.1186/1742-4682-10-5

Published: 17 January 2013

Abstract

The hematopoietic stem cell (HSC) system is a demand control system, with the demand coming from the organism, since the products of the common myeloid and lymphoid progenitor (CMP, CLP respectively) cells are essential for activity and defense against disease. We show how ideas from population biology (combining population dynamics and evolutionary considerations) can illuminate the feedback control of the HSC system by the fully differentiated products, which has recently been verified experimentally. We develop models for the penultimate differentiation of HSC Multipotent Progenitors (MPPs) into CLP and CMP and introduce two concepts from population biology into stem cell biology. The first concept is the Multipotent Progenitor Commitment Response (MPCR) which is the probability that a multipotent progenitor cell follows a CLP route rather than a CMP route. The second concept is the link between the MPCR and a measure of Darwinian fitness associated with organismal performance and the levels of differentiated lymphoid and myeloid cells. We show that many MPCRs are consistent with homeostasis, but that they will lead to different dynamics of cells and signals following a wound or injury and thus have different consequences for Darwinian fitness. We show how coupling considerations of life history to dynamics of the HSC system and its products allows one to compute the selective pressures on cellular processes. We discuss ways that this framework can be used and extended.

Keywords:
Hematopoieitic stem cell; Multipotent progenitor; Common lymphoid progenitor; Common myeloid progenitor; Darwinian fitness; Natural selection; Population dynamics