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Combining Intravital Fluorescent Microscopy IVFM with Genetic Models to Study Engraftment Dynamics of Hematopoietic Cells to Bone Marrow Niches
Published on: March 21, 2017
A theory of evolutionary dynamics on any complex population structure reveals stem cell niche architecture as a
Yang Ping Kuo1,2, César Nombela-Arrieta3, Oana Carja4
1Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA.
Abstract:
How the spatial arrangement of a population shapes its evolutionary dynamics has been of long-standing interest in population genetics. Most previous studies assume a small number of demes or symmetrical structures that, most often, act as well-mixed populations. Other studies use network theory to study more heterogeneous spatial structures, however they usually assume small, regular networks, or strong constraints on the strength of selection considered. Here we build network generation algorithms, conduct evolutionary simulations and derive general analytic approximations for probabilities of fixation in populations with complex spatial structure. We build a unifying evolutionary theory across network families and derive the relevant selective parameter, which is a combination of network statistics, predictive of evolutionary dynamics. We also illustrate how to link this theory with novel datasets of spatial organization and use recent imaging data to build the cellular spatial networks of the stem cell niches of the bone marrow. Across a wide variety of parameters, we find these networks to be strong suppressors of selection, delaying mutation accumulation in this tissue. We also find that decreases in stem cell population size also decrease the suppression strength of the tissue spatial structure.
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