title: Lineages, cell types and functional states: a genomic view.
abstract: Cellular differentiation progresses through an ordered cascade of events involving cell autonomous and micro-environment regulated expression or activation of transcription factors (TFs). Lineage-determining and stimulus-activated TFs collaborate in specifying the transcriptional programs of differentiating cells through the establishment of appropriate genomic repertoires of active or poised cis-regulatory elements, which can eventually be altered by environmental changes to generate transient or persistent functional states. Here, we rationalize available genomic and functional data into a mechanistic model whereby terminal differentiation proceeds first through the establishment of a regulatory landscape that is broadly shared among all cell types within a given lineage; and then through the selective activation of a more restricted set of regulatory elements that specify the unique transcriptional outputs of individual cell types. In this scheme, the interplay between cell-autonomous and microenvironment-regulated TFs is highly complex, with several documented variants.
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (IEO), Via Adamello 16, 20139 Milan, Italy. Electronic address: renato.ostuni@ieo.eu.
authors.forename: Renato
authors.initials: R
authors.lastname: Ostuni
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Natoli
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D053263:Gene Regulatory Networks; D023281:Genomics; D006801:Humans; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors