title: Transcription factor heterogeneity in pluripotent stem cells: a stochastic advantage.
abstract: When pluripotent cells are exposed to a uniform culture environment they routinely display heterogeneous gene expression. Aspects of this heterogeneity, such as Nanog expression, are linked to differences in the propensity of individual cells to either self-renew or commit towards differentiation. Recent findings have provided new insight into the underlying causes of this heterogeneity, which we summarise here using Nanog, a key regulator of pluripotency, as a model gene. We discuss the role of transcription factor heterogeneity in facilitating the intrinsically dynamic and stochastic nature of the pluripotency network, which in turn provides a potential benefit to a population of cells that needs to balance cell fate decisions.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM U964, Université de Strasbourg, Cité Universitaire de Strasbourg, Illkirch F-67404, France metp@igbmc.fr ichambers@ed.ac.uk.
authors.forename: Maria-Elena
authors.initials: ME
authors.lastname: Torres-Padilla
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK metp@igbmc.fr ichambers@ed.ac.uk.
authors.forename: Ian
authors.initials: I
authors.lastname: Chambers
mesh_terms: D000483:Alleles; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002467:Cell Nucleus / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008962:Models, Theoretical; D000071317:Nanog Homeobox Protein; D039904:Pluripotent Stem Cells / Q000166:cytology*; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013269:Stochastic Processes; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D014157:Transcription Factors
keywords: Embryonic stem cell (ESC); Epiblast; Heterogeneity; Monoallelic; Pluripotency; Transcription