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Systems mapping for hematopoietic progenitor cell heterogeneity.

Zhou L, Shen Y, Jiang L, Yin D, Guo J, Zheng H, Sun H, Wu R, Guo Y - PLoS ONE (2015)

Bottom Line: The heterogeneity of hematopoietic progenitor cells has an effect on their differentiation potential and lineage choices.This model not only considers the traditional QTLs, but also indicates the methylated QTLs that can illustrate non-genetic individual differences.It has significant implications for probing the molecular, genetic and epigenetic mechanisms of hematopoietic progenitor cell heterogeneity.

View Article: PubMed Central - PubMed

Affiliation: Center for Computational Biology, Beijing Forestry University, Beijing, People's Republic of China.

ABSTRACT
Cells with the same genotype growing under the same conditions can show different phenotypes, which is known as "population heterogeneity". The heterogeneity of hematopoietic progenitor cells has an effect on their differentiation potential and lineage choices. However, the genetic mechanisms governing population heterogeneity remain unclear. Here, we present a statistical model for mapping the quantitative trait locus (QTL) that affects hematopoietic cell heterogeneity. This strategy, termed systems mapping, integrates a system of differential equations into the framework for systems mapping, allowing hypotheses regarding the interplay between genetic actions and cell heterogeneity to be tested. A simulation approach based on cell heterogeneity dynamics has been designed to test the statistical properties of the model. This model not only considers the traditional QTLs, but also indicates the methylated QTLs that can illustrate non-genetic individual differences. It has significant implications for probing the molecular, genetic and epigenetic mechanisms of hematopoietic progenitor cell heterogeneity.

No MeSH data available.


Related in: MedlinePlus

Estimated and true curves of systems mapping for the nonlinear progenitor cell transition dynamics model.The curves show a putative QTL having six genotypes, QQ, Qq, Qq+, qq, qq+, and q+q+, as indicated by colors in a natural population of 400 assuming heritability H2 = 0.05 (a), H2 = 0.1 (b), and H2 = 0.2 (c), respectively. The broad consistency between the estimated (solid) and true curves (broken) suggests that the model provides a good estimate of the dynamic system.
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pone.0126937.g004: Estimated and true curves of systems mapping for the nonlinear progenitor cell transition dynamics model.The curves show a putative QTL having six genotypes, QQ, Qq, Qq+, qq, qq+, and q+q+, as indicated by colors in a natural population of 400 assuming heritability H2 = 0.05 (a), H2 = 0.1 (b), and H2 = 0.2 (c), respectively. The broad consistency between the estimated (solid) and true curves (broken) suggests that the model provides a good estimate of the dynamic system.

Mentions: The six QTL genotypes QQ, Qq, Qq+, qq, qq+, and q+q+ are each hypothesized to have different response curves for different human populations. Figs 3 and 4 illustrate different forms of the cell population transition for six QTL genotypes, QQ, Qq, Qq+, qq, qq+, and q+q+, under different heritabilities (0.05, 0.1 and 0.2) with size 400 populations, with the transitional values given in Table 3 for the linear model and Table 5 for the nonlinear model. Pronounced differences among the genotypes suggest that the QTL may affect cell transitions, resulting in different cellular phenotypes. Meanwhile, we considered the methylated QTL status (Qq+, qq+, and q+q+), which could illustrate phenotypic differences among cells with the same DNA sequences. The cell transition values can be estimated from the model. The model displays great power in detecting a QTL responsible for cell transitions using the associated marker. The trajectories of additive and dominant effects of subpopulations x1 and x2 are shown as Figs 5 and 6 for the linear model and nonlinear model, respectively. We could observe the genetic architecture of the transition dynamics of the two subpopulation cells.


Systems mapping for hematopoietic progenitor cell heterogeneity.

Zhou L, Shen Y, Jiang L, Yin D, Guo J, Zheng H, Sun H, Wu R, Guo Y - PLoS ONE (2015)

Estimated and true curves of systems mapping for the nonlinear progenitor cell transition dynamics model.The curves show a putative QTL having six genotypes, QQ, Qq, Qq+, qq, qq+, and q+q+, as indicated by colors in a natural population of 400 assuming heritability H2 = 0.05 (a), H2 = 0.1 (b), and H2 = 0.2 (c), respectively. The broad consistency between the estimated (solid) and true curves (broken) suggests that the model provides a good estimate of the dynamic system.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4430299&req=5

pone.0126937.g004: Estimated and true curves of systems mapping for the nonlinear progenitor cell transition dynamics model.The curves show a putative QTL having six genotypes, QQ, Qq, Qq+, qq, qq+, and q+q+, as indicated by colors in a natural population of 400 assuming heritability H2 = 0.05 (a), H2 = 0.1 (b), and H2 = 0.2 (c), respectively. The broad consistency between the estimated (solid) and true curves (broken) suggests that the model provides a good estimate of the dynamic system.
Mentions: The six QTL genotypes QQ, Qq, Qq+, qq, qq+, and q+q+ are each hypothesized to have different response curves for different human populations. Figs 3 and 4 illustrate different forms of the cell population transition for six QTL genotypes, QQ, Qq, Qq+, qq, qq+, and q+q+, under different heritabilities (0.05, 0.1 and 0.2) with size 400 populations, with the transitional values given in Table 3 for the linear model and Table 5 for the nonlinear model. Pronounced differences among the genotypes suggest that the QTL may affect cell transitions, resulting in different cellular phenotypes. Meanwhile, we considered the methylated QTL status (Qq+, qq+, and q+q+), which could illustrate phenotypic differences among cells with the same DNA sequences. The cell transition values can be estimated from the model. The model displays great power in detecting a QTL responsible for cell transitions using the associated marker. The trajectories of additive and dominant effects of subpopulations x1 and x2 are shown as Figs 5 and 6 for the linear model and nonlinear model, respectively. We could observe the genetic architecture of the transition dynamics of the two subpopulation cells.

Bottom Line: The heterogeneity of hematopoietic progenitor cells has an effect on their differentiation potential and lineage choices.This model not only considers the traditional QTLs, but also indicates the methylated QTLs that can illustrate non-genetic individual differences.It has significant implications for probing the molecular, genetic and epigenetic mechanisms of hematopoietic progenitor cell heterogeneity.

View Article: PubMed Central - PubMed

Affiliation: Center for Computational Biology, Beijing Forestry University, Beijing, People's Republic of China.

ABSTRACT
Cells with the same genotype growing under the same conditions can show different phenotypes, which is known as "population heterogeneity". The heterogeneity of hematopoietic progenitor cells has an effect on their differentiation potential and lineage choices. However, the genetic mechanisms governing population heterogeneity remain unclear. Here, we present a statistical model for mapping the quantitative trait locus (QTL) that affects hematopoietic cell heterogeneity. This strategy, termed systems mapping, integrates a system of differential equations into the framework for systems mapping, allowing hypotheses regarding the interplay between genetic actions and cell heterogeneity to be tested. A simulation approach based on cell heterogeneity dynamics has been designed to test the statistical properties of the model. This model not only considers the traditional QTLs, but also indicates the methylated QTLs that can illustrate non-genetic individual differences. It has significant implications for probing the molecular, genetic and epigenetic mechanisms of hematopoietic progenitor cell heterogeneity.

No MeSH data available.


Related in: MedlinePlus