Monday, June 3, 2013

A deterministic model for the occurrence and dynamics of multiple mutations in hierarchically organized tissues


A nice follow on paper to their recent work in PLoS Computational Biology studying the deterministic dynamics of mutant clones in hierarchically structured (stem cell-driven) populations.  They derive closed form solutions describing the make up and diversity of tissues derived from this architecture and show specifically that that dynamics of a hierarchically structured tissue suppress the possibility of multiply mutated cells, and discuss the ramifications of this in regards to acute lymphoblastic leukemia of childhood.


A deterministic model for the occurrence and dynamics of multiple mutations in hierarchically organized tissues

We model a general, hierarchically organized tissue by a multi compartment approach, allowing any number of mutations within a cell. We derive closed solutions for the deterministic clonal dynamics and the reproductive capacity of single clones. Our results hold for the average dynamics in a hierarchical tissue characterized by an arbitrary combination of proliferation parameters.