title: Gene expression variability as a unifying element of the pluripotency network.
abstract: Heterogeneity is a hallmark of stem cell populations, in part due to the molecular differences between cells undergoing self-renewal and those poised to differentiate. We examined phenotypic and molecular heterogeneity in pluripotent stem cell populations, using public gene expression data sets. A high degree of concordance was observed between global gene expression variability and the reported heterogeneity of different human pluripotent lines. Network analysis demonstrated that low-variability genes were the most highly connected, suggesting that these are the most stable elements of the gene regulatory network and are under the highest regulatory constraints. Known drivers of pluripotency were among these, with lowest expression variability of POU5F1 in cells with the highest capacity for self-renewal. Variability of gene expression provides a reliable measure of phenotypic and molecular heterogeneity and predicts those genes with the highest degree of regulatory constraint within the pluripotency network.
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Brisbane QSLD 4072, Australia.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mason
authors.affiliation: The Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Mar
authors.affiliation: Materials Science and Engineering, CSIRO, Clayton VIC 3168, Australia.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Laslett
authors.affiliation: The University of Melbourne, Florey Neuroscience and Mental Health Institute, and Walter and Eliza Hall Institute of Medical Research, Parkville VIC 3010, Australia.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Pera
authors.affiliation: Dana-Farber Cancer Institute, Harvard University, Boston, MA 02215 USA.
authors.forename: John
authors.initials: J
authors.lastname: Quackenbush
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Brisbane QSLD 4072, Australia.
authors.forename: Ernst
authors.initials: E
authors.lastname: Wolvetang
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Brisbane QSLD 4072, Australia; Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK. Electronic address: c.wells@uq.edu.au.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Wells
mesh_terms: D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D053263:Gene Regulatory Networks; D006801:Humans; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D059467:Transcriptome
chemical_list: D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human