title: Gene-pair expression signatures reveal lineage control.
abstract: The distinct cell types of multicellular organisms arise owing 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 curated human expression data comprising 166 cell types and 2,602 transcription-regulating genes and developed a data-driven method for identifying putative determinants of cell fate built around the concept of expression reversal of gene pairs, such as those participating in toggle-switch circuits. This approach allows us to organize the cell types into their ontogenic lineage relationships. Our method identifies genes in regulatory circuits that control neuronal fate, pluripotency and blood cell differentiation, and it may be useful for prioritizing candidate factors for direct conversion of cell fate.
authors.affiliation: Life Sciences Research Unit, University of Luxembourg, Luxembourg, Luxembourg.
authors.forename: Merja
authors.initials: M
authors.lastname: Heinäniemi
authors.forename: Matti
authors.initials: M
authors.lastname: Nykter
authors.forename: Roger
authors.initials: R
authors.lastname: Kramer
authors.forename: Anke
authors.initials: A
authors.lastname: Wienecke-Baldacchino
authors.forename: Lasse
authors.initials: L
authors.lastname: Sinkkonen
authors.forename: Joseph Xu
authors.initials: JX
authors.lastname: Zhou
authors.forename: Richard
authors.initials: R
authors.lastname: Kreisberg
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Kauffman
authors.forename: Sui
authors.initials: S
authors.lastname: Huang
authors.forename: Ilya
authors.initials: I
authors.lastname: Shmulevich
mesh_terms: D002454:Cell Differentiation; D019070:Cell Lineage; D053263:Gene Regulatory Networks; D006801:Humans; D059467:Transcriptome