Abstract
One of the fundamental mysteries in biology is to grasp how a cell can choose a specific cellular process in coordinating complex multi-molecular interactions through DNA, RNA, proteins and metabolites. We investigated the existence of guiding principles in gene expression dynamics for three distinct processes: i) the innate immune response of macrophages to lipopolysaccharide (LPS) stimulation, ii) interleukin 12 (IL-12) and IL-4 stimulated naive CD4+ T cell differentiation into helper T1 and T2 cells, and iii) HL-60 cell differentiation into neutrophil. We found that for all processes, forming groups of genes reduces gene expression fluctuations, revealing the emergent hidden collective genome-wide (global) expression dynamics and their biological roles. This demonstrates an important role of lowly expressed genes, which have been considered insignificant and noisy, as key players for collective global dynamics. Moreover, in neutrophil differentiation, there are specific gene ensembles (collectively named "genome vehicle") responsible for the cell fate, and the collective motion of lowly and moderately variable genes within the genome vehicle guides whole genome expression dynamics to the neutrophil cell state. Elucidation of biophysical origin for the global guiding principle might provide a breakthrough understanding of how a genome can control cellular processes such as cell fate and differentiation.
| Original language | English |
|---|---|
| Title of host publication | 2012 ICME International Conference on Complex Medical Engineering, CME 2012 Proceedings |
| Pages | 744-749 |
| Number of pages | 6 |
| DOIs | |
| Publication status | Published - 2012 |
| Event | 6th International Conference on Complex Medical Engineering, CME 2012 - Kobe, Japan Duration: 2012 Jul 1 → 2012 Jul 4 |
Other
| Other | 6th International Conference on Complex Medical Engineering, CME 2012 |
|---|---|
| Country | Japan |
| City | Kobe |
| Period | 12/7/1 → 12/7/4 |
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Keywords
- biological attractor
- cell differentiation
- gene expression dynamics
- global regulation
- innate immune
ASJC Scopus subject areas
- Biomedical Engineering
Cite this
Robust global regulations of gene expression in biological processes : A major driver of cell fate decision revealed. / Tsuchiya, Masa; Tomita, Masaru; Hashimoto, Midori.
2012 ICME International Conference on Complex Medical Engineering, CME 2012 Proceedings. 2012. p. 744-749 6275649.Research output: Chapter in Book/Report/Conference proceeding › Conference contribution
}
TY - GEN
T1 - Robust global regulations of gene expression in biological processes
T2 - A major driver of cell fate decision revealed
AU - Tsuchiya, Masa
AU - Tomita, Masaru
AU - Hashimoto, Midori
PY - 2012
Y1 - 2012
N2 - One of the fundamental mysteries in biology is to grasp how a cell can choose a specific cellular process in coordinating complex multi-molecular interactions through DNA, RNA, proteins and metabolites. We investigated the existence of guiding principles in gene expression dynamics for three distinct processes: i) the innate immune response of macrophages to lipopolysaccharide (LPS) stimulation, ii) interleukin 12 (IL-12) and IL-4 stimulated naive CD4+ T cell differentiation into helper T1 and T2 cells, and iii) HL-60 cell differentiation into neutrophil. We found that for all processes, forming groups of genes reduces gene expression fluctuations, revealing the emergent hidden collective genome-wide (global) expression dynamics and their biological roles. This demonstrates an important role of lowly expressed genes, which have been considered insignificant and noisy, as key players for collective global dynamics. Moreover, in neutrophil differentiation, there are specific gene ensembles (collectively named "genome vehicle") responsible for the cell fate, and the collective motion of lowly and moderately variable genes within the genome vehicle guides whole genome expression dynamics to the neutrophil cell state. Elucidation of biophysical origin for the global guiding principle might provide a breakthrough understanding of how a genome can control cellular processes such as cell fate and differentiation.
AB - One of the fundamental mysteries in biology is to grasp how a cell can choose a specific cellular process in coordinating complex multi-molecular interactions through DNA, RNA, proteins and metabolites. We investigated the existence of guiding principles in gene expression dynamics for three distinct processes: i) the innate immune response of macrophages to lipopolysaccharide (LPS) stimulation, ii) interleukin 12 (IL-12) and IL-4 stimulated naive CD4+ T cell differentiation into helper T1 and T2 cells, and iii) HL-60 cell differentiation into neutrophil. We found that for all processes, forming groups of genes reduces gene expression fluctuations, revealing the emergent hidden collective genome-wide (global) expression dynamics and their biological roles. This demonstrates an important role of lowly expressed genes, which have been considered insignificant and noisy, as key players for collective global dynamics. Moreover, in neutrophil differentiation, there are specific gene ensembles (collectively named "genome vehicle") responsible for the cell fate, and the collective motion of lowly and moderately variable genes within the genome vehicle guides whole genome expression dynamics to the neutrophil cell state. Elucidation of biophysical origin for the global guiding principle might provide a breakthrough understanding of how a genome can control cellular processes such as cell fate and differentiation.
KW - biological attractor
KW - cell differentiation
KW - gene expression dynamics
KW - global regulation
KW - innate immune
UR - http://www.scopus.com/inward/record.url?scp=84867651352&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867651352&partnerID=8YFLogxK
U2 - 10.1109/ICCME.2012.6275649
DO - 10.1109/ICCME.2012.6275649
M3 - Conference contribution
SN - 9781467316163
SP - 744
EP - 749
BT - 2012 ICME International Conference on Complex Medical Engineering, CME 2012 Proceedings
ER -