Systems mapping for hematopoietic progenitor cell heterogeneity

PLoS One. 2015 May 13;10(5):e0126937. doi: 10.1371/journal.pone.0126937. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Chromosome Mapping
  • DNA Methylation
  • Epigenesis, Genetic
  • Genotype
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Models, Genetic
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci

Grants and funding

The National Natural Science Foundation of China (31370669, 30900854) and the Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (KLRB201308). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.