Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 12, Pages 4598-4603Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1218682110
Keywords
NT5E/CD73; pluripotency
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Funding
- National Cancer Institute [CA097214, CA107584, ES017154, CA135626]
- Avon Foundation [07-2007-074]
- Cancer League, Inc.
- California Institute for Regenerative Medicine [RS1-00444-1]
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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.
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