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Genome-Wide Analysis Reveals the Unique Stem Cell Identity of Human Amniocytes

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  • Colin T Maguire
  • Bradley L Demarest
  • Jonathon T Hill
  • James D Palmer
  • Arthur R Brothman
  • H Joseph Yost
  • Maureen L Condic

Abstract

Human amniotic fluid contains cells that potentially have important stem cell characteristics, yet the programs controlling their developmental potency are unclear. Here, we provide evidence that amniocytes derived from multiple patients are marked by heterogeneity and variability in expression levels of pluripotency markers. Clonal analysis from multiple patients indicates that amniocytes have large pools of self-renewing cells that have an inherent property to give rise to a distinct amniocyte phenotype with a heterogeneity of pluripotent markers. Significant to their therapeutic potential, genome-wide profiles are distinct at different gestational ages and times in culture, but do not differ between genders. Based on hierarchical clustering and differential expression analyses of the entire transcriptome, amniocytes express canonical regulators associated with pluripotency and stem cell repression. Their profiles are distinct from human embryonic stem cells (ESCs), induced-pluripotent stem cells (iPSCs), and newborn foreskin fibroblasts. Amniocytes have a complex molecular signature, coexpressing trophoblastic, ectodermal, mesodermal, and endodermal cell-type-specific regulators. In contrast to the current view of the ground state of stem cells, ESCs and iPSCs also express high levels of a wide range of cell-type-specific regulators. The coexpression of multilineage differentiation markers combined with the strong expression of a subset of ES cell repressors in amniocytes suggests that these cells have a distinct phenotype that is unlike any other known cell-type or lineage.

Suggested Citation

  • Colin T Maguire & Bradley L Demarest & Jonathon T Hill & James D Palmer & Arthur R Brothman & H Joseph Yost & Maureen L Condic, 2013. "Genome-Wide Analysis Reveals the Unique Stem Cell Identity of Human Amniocytes," PLOS ONE, Public Library of Science, vol. 8(1), pages 1-16, January.
    • Handle: RePEc:plo:pone00:0053372
    DOI: 10.1371/journal.pone.0053372
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    References listed on IDEAS

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    1. Ian Chambers & Jose Silva & Douglas Colby & Jennifer Nichols & Bianca Nijmeijer & Morag Robertson & Jan Vrana & Ken Jones & Lars Grotewold & Austin Smith, 2007. "Nanog safeguards pluripotency and mediates germline development," Nature, Nature, vol. 450(7173), pages 1230-1234, December.
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    1. Hans-Juergen Schulten & Deema Hussein, 2019. "Array expression meta-analysis of cancer stem cell genes identifies upregulation of PODXL especially in DCC low expression meningiomas," PLOS ONE, Public Library of Science, vol. 14(5), pages 1-20, May.

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