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Internalization of REIC/Dkk-3 protein by induced pluripotent stem cell-derived embryoid bodies and extra-embryonic

Ken Kataoka1, Masakiyo Sakaguchi, Kun Peng Li

  • 1Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, Japan.

International Journal of Molecular Medicine
|November 3, 2010
PubMed

Insights

REIC/Dkk-3 protein is internalized by specific cell types during development, particularly in extra-embryonic tissues. This finding helps understand REIC/Dkk-3

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Cancer Research

Background:

  • REIC/Dkk-3 gene is downregulated in human tumors.
  • Adenovirus-mediated REIC/Dkk-3 (Ad-REIC) shows anti-cancer effects via ER stress and IL-7 induction.
  • The physiological function and receptors of REIC/Dkk-3 remain largely unknown.

Purpose of the Study:

  • To investigate the cellular uptake and potential receptors of secreted REIC/Dkk-3 protein.
  • To explore the internalization patterns of REIC/Dkk-3 in stem cells and developmental tissues.

Main Methods:

  • Incubation of Cy3-labeled recombinant REIC/Dkk-3 protein with various cell lines, including mouse induced pluripotent stem (iPS) cells.
  • Analysis of REIC/Dkk-3 internalization in iPS cell colonies, embryoid bodies (EBs), and embryonic tissues at different developmental stages (4.5 dpc and 16.5 dpc).
  • Confirmation of the internalization mechanism as endocytosis.

Main Results:

  • REIC/Dkk-3 protein was uniquely internalized by peripheral cells of iPS colonies and differentiated cells at the periphery of EBs.
  • In contrast, Dkk-1 was internalized by undifferentiated cells at the center of EBs.
  • REIC/Dkk-3 internalization in developmental tissues was restricted to extra-embryonic lineages, including the trophectoderm and chorionic membrane.

Conclusions:

  • REIC/Dkk-3 exhibits specific internalization patterns in stem cells and during early embryonic development.
  • These findings suggest distinct roles for REIC/Dkk-3 and Dkk-1 in cellular differentiation.
  • The study provides foundational knowledge for identifying REIC/Dkk-3 receptors and understanding its biological functions.

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