Cell Isolation Induces Fate Changes of Bone Marrow Mesenchymal Cells Leading to Loss or Alternatively to Acquisition of New Differentiation Potentials

Authors

  • Ofer Shoshani,

    Corresponding author
    1. Department of Molecular Cell Biology, Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel
    • Correspondence: Dov Zipori, Ph.D., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel. Telephone: 972-8-934-2484; Fax: 972-8-934-4125; e-mail: dov.zipori@weizmann.ac.il; or Ofer Shoshani, Ph.D., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel. Telephone: 972-8-934-2484; Fax: 972-8-934-4125; e-mail: ofsher@hotmail.com

    Search for more papers by this author
  • Orly Ravid,

    1. Department of Molecular Cell Biology, Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel
    Search for more papers by this author
  • Hassan Massalha,

    1. Department of Molecular Cell Biology, Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel
    Search for more papers by this author
  • Alla Aharonov,

    1. Department of Molecular Cell Biology, Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel
    Search for more papers by this author
  • Yossi Ovadya,

    1. Department of Molecular Cell Biology, Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel
    Search for more papers by this author
  • Meirav Pevsner-Fischer,

    1. Department of Molecular Cell Biology, Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel
    Search for more papers by this author
  • Dena Leshkowitz,

    1. Bioinformatics Unit, Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel
    Search for more papers by this author
  • Dov Zipori

    Corresponding author
    1. Department of Molecular Cell Biology, Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel
    • Correspondence: Dov Zipori, Ph.D., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel. Telephone: 972-8-934-2484; Fax: 972-8-934-4125; e-mail: dov.zipori@weizmann.ac.il; or Ofer Shoshani, Ph.D., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel. Telephone: 972-8-934-2484; Fax: 972-8-934-4125; e-mail: ofsher@hotmail.com

    Search for more papers by this author

Abstract

Mesenchymal stromal cell populations include a fraction, termed mesenchymal stem cells, exhibiting multipotency. Other cells within this population possess a lesser differentiation range. This was assumed to be due to a mesenchymal cellular cascade topped by a multipotent cell, which gives rise to progeny with diminishing differentiation potentials. Here, we show that mesenchymal cells, a priori exhibiting a limited differentiation potential, may gain new capacities and become multipotent following single-cell isolation. These fate changes were accompanied by upregulation of differentiation promoting genes, many of which also became H4K20me1 methylated. Early events in the process included TGFβ and Wnt modulation, and downregulation of hypoxia signaling. Indeed, hypoxic conditions inhibited the observed cell changes. Overall, cell isolation from neighboring partners caused major molecular changes and particularly, a newly established epigenetic state, ultimately leading to the acquisition of new differentiation potentials and an altered cell fate. Stem Cells 2014;32:2008–2020

Ancillary