[en] The distinct cell types of multicellular organisms arise due to constraints imposed by gene regulatory networks on the collective change of gene expression across the genome, creating self-stabilizing expression states, or attractors. We compiled a resource of curated human expression data comprising 166 cell types and 2,602 transcription regulating genes and developed a data driven method built around the concept of expression reversal defined at the level of gene pairs, such as those participating in toggle switch circuits. This approach allows us to organize the cell types into their ontogenetic lineage-relationships and to reflect regulatory relationships among genes that explain their ability to function as determinants of cell fate. We show that this method identifies genes belonging to regulatory circuits that control neuronal fate, pluripotency and blood cell differentiation, thus offering a novel large-scale perspective on lineage specification.
Research center :
Luxembourg Centre for Systems Biomedicine (LCSB): Experimental Neurobiology (Balling Group) LSRU
Disciplines :
Life sciences: Multidisciplinary, general & others
Identifiers :
UNILU:UL-ARTICLE-2013-144
Author, co-author :
HEINÄNIEMI, Merja ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Nykter, Matti; Tampere University of Technology > Department of Signal Processing
Kramer, Roger; Institute for Systems Biology
WIENECKE, Anke ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
SINKKONEN, Lasse ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Zhou, J. X.; University of Calgary - U of C. > Institute for Biocomplexity and Informatics
Kreisberg, Richard; Institute for Systems Biology
Kauffman, Stuart A.; Institute for Systems Biology
Huang, Sui; Institute for Systems Biology
Shmulevich, Ilya; Institute for Systems Biology
External co-authors :
yes
Language :
English
Title :
Gene-pair expression signatures reveal lineage control