title: Single-cell gene expression profiles define self-renewing, pluripotent, and lineage primed states of human pluripotent stem cells.
abstract: Pluripotent stem cells display significant heterogeneity in gene expression, but whether this diversity is an inherent feature of the pluripotent state remains unknown. Single-cell gene expression analysis in cell subsets defined by surface antigen expression revealed that human embryonic stem cell cultures exist as a continuum of cell states, even under defined conditions that drive self-renewal. The majority of the population expressed canonical pluripotency transcription factors and could differentiate into derivatives of all three germ layers. A minority subpopulation of cells displayed high self-renewal capacity, consistently high transcripts for all pluripotency-related genes studied, and no lineage priming. This subpopulation was characterized by its expression of a particular set of intercellular signaling molecules whose genes shared common regulatory features. Our data support a model of an inherently metastable self-renewing population that gives rise to a continuum of intermediate pluripotent states, which ultimately become primed for lineage specification.
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA ; University of Melbourne, Melbourne, 3010 VIC, Australia.
authors.forename: Shelley R
authors.initials: SR
authors.lastname: Hough
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Thornton
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, 4072 QLD, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mason
authors.affiliation: Department of Systems and Computational Biology and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Mar
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, 4072 QLD, Australia.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Wells
authors.affiliation: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA ; University of Melbourne, Walter and Eliza Hall Institute of Medical Research, Florey Institute of Neuroscience and Mental Health, Melbourne, 3010 VIC, Australia.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Pera
mesh_terms: D002460:Cell Line; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors