title: Rare somatic cells from human breast tissue exhibit extensive lineage plasticity.
abstract: We identified cell surface markers associated with repression of p16(INK4a)/cyclin-dependent kinase inhibitor 2A(CDKN2A), a critical determinant in the acquisition of a plastic state. These cell surface markers allowed direct isolation of rare cells from healthy human breast tissue that exhibit extensive lineage plasticity. This subpopulation is poised to transcribe plasticity markers, OCT3/4, SOX2, and NANOG, at levels similar to those measured in human embryonic stem cells and to acquire a plastic state sensitive to environmental programming. In vitro, in vivo, and teratoma assays demonstrated that either a directly sorted (uncultured) or a single-cell (clonogenic) cell population from primary tissue can differentiate into functional derivatives of each germ layer, ectodermal, endodermal, and mesodermal. In contrast to other cells that express OCT3/4, SOX2, and NANOG, these human endogenous plastic somatic cells are mortal, express low telomerase activity, expand for an extensive but finite number of population doublings, and maintain a diploid karyotype before arresting in G1.
authors.affiliation: Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA 94143-0511, USA.
authors.forename: Somdutta
authors.initials: S
authors.lastname: Roy
authors.forename: Philippe
authors.initials: P
authors.lastname: Gascard
authors.forename: Nancy
authors.initials: N
authors.lastname: Dumont
authors.forename: Jianxin
authors.initials: J
authors.lastname: Zhao
authors.forename: Deng
authors.initials: D
authors.lastname: Pan
authors.forename: Sarah
authors.initials: S
authors.lastname: Petrie
authors.forename: Marta
authors.initials: M
authors.lastname: Margeta
authors.forename: Thea D
authors.initials: TD
authors.lastname: Tlsty
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D001940:Breast / Q000166:cytology* / Q000378:metabolism*; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000502:physiology; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis
chemical_list: D000943:Antigens, Differentiation; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors