Collective dynamics of specific gene ensembles crucial for neutrophil differentiation

The existence of genome vehicles revealed

Masa Tsuchiya, Vincent Piras, Alessandro Giuliani, Masaru Tomita, Kumar Selvarajoo

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Cell fate decision remarkably generates specific cell differentiation path among the multiple possibilities that can arise through the complex interplay of high-dimensional genome activities. The coordinated action of thousands of genes to switch cell fate decision has indicated the existence of stable attractors guiding the process. However, origins of the intracellular mechanisms that create "cellular attractor" still remain unknown. Here, we examined the collective behavior of genome-wide expressions for neutrophil differentiation through two different stimuli, dimethyl sulfoxide (DMSO) and alltrans- retinoic acid (atRA). To overcome the difficulties of dealing with single gene expression noises, we grouped genes into ensembles and analyzed their expression dynamics in correlation space defined by Pearson correlation and mutual information. The standard deviation of correlation distributions of gene ensembles reduces when the ensemble size is increased following the inverse square root law, for both ensembles chosen randomly from whole genome and ranked according to expression variances across time. Choosing the ensemble size of 200 genes, we show the two probability distributions of correlations of randomly selected genes for atRA and DMSO responses overlapped after 48 hours, defining the neutrophil attractor. Next, tracking the ranked ensembles' trajectories, we noticed that only certain, not all, fall into the attractor in a fractal-like manner. The removal of these genome elements from the whole genomes, for both atRA and DMSO responses, destroys the attractor providing evidence for the existence of specific genome elements (named "genome vehicle") responsible for the neutrophil attractor. Notably, within the genome vehicles, genes with low or moderate expression changes, which are often considered noisy and insignificant, are essential components for the creation of the neutrophil attractor. Further investigations along with our findings might provide a comprehensive mechanistic view of cell fate decision.

Original languageEnglish
Article numbere12116
JournalPLoS One
Volume5
Issue number8
DOIs
Publication statusPublished - 2010

Fingerprint

neutrophils
Neutrophils
Genes
Genome
genome
retinoic acid
dimethyl sulfoxide
genes
Dimethyl Sulfoxide
Tretinoin
Switch Genes
Fractals
group behavior
probability distribution
cells
cell differentiation
trajectories
Noise
Cell Differentiation
Gene Expression

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Collective dynamics of specific gene ensembles crucial for neutrophil differentiation : The existence of genome vehicles revealed. / Tsuchiya, Masa; Piras, Vincent; Giuliani, Alessandro; Tomita, Masaru; Selvarajoo, Kumar.

In: PLoS One, Vol. 5, No. 8, e12116, 2010.

Research output: Contribution to journalArticle

Tsuchiya, Masa ; Piras, Vincent ; Giuliani, Alessandro ; Tomita, Masaru ; Selvarajoo, Kumar. / Collective dynamics of specific gene ensembles crucial for neutrophil differentiation : The existence of genome vehicles revealed. In: PLoS One. 2010 ; Vol. 5, No. 8.
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