Figure 1
From: Heterogeneous Structure of Stem Cells Dynamics: Statistical Models and Quantitative Predictions
Heterogeneity in Stem Cell Populations.
(a) Stem cell populations are comprised of mitotically active (dividing) and mitotically inactive (nondividing: quiescent cells, terminally differentiated cells, senescent cells and dying cells). (b) Proliferative heterogeneity results from asynchrony in life stage which leads, in part, to the presence of these subpopulations. (c) More specifically, asymmetric divisions and fates or symmetric divisions1,2,3,4,5,6,7,8,9 lead to different subpopulations. Intrinsic or extrinsic factors play a role in whether the daughter cells are different due to internal cues or environmental cues. (d) An example of development of heterogeneity from intrinsic cell differences. Asymmetry in DNA strand segregation would allow for stem cell self-renewal. The (blue) stem cell would retain the oldest DNA strands. This cartoon shows segregation of 1 chromosome: the oldest/grandparent strand is blue and designated 1.0 and the parent strand (a copy of the grandparent strand) is red and designated 1.1. All other copies are dashed lines and designated copy numbers are 1.1.1, 1.1.1.1, 1.1.1.1.1 etc. If non-random strand segregation occurs among all chromatids in the cell, the result is asymmetric divisions and self-renewal of the stem cell. We show here how heterogeneity could result in the expanding population. If distinct phenotypes occur based on the DNA strand copy numbers, then these phenotypes can be categorized based on the template and copy number. E.g., after the 3 divisions shown in the lineage tree above, there would be 1 stem cell (1.0 and 1.1 strands, p0 phenotype), 3 pI cells would have (1.1/1.1.1 stands), 3 pII cells (1.1.1/1.1.1.1) and 1 pIII cell (1.1.1.1/1.1.1.1.1).
