Open AccessCell Isolation Induces Fate Changes of Bone Marrow Mesenchymal Cells Leading to Loss or Alternatively to Acquisition of New Differentiation Potentials
Author(s) -
Shoshani Ofer,
Ravid Orly,
Massalha Hassan,
Aharonov Alla,
Ovadya Yossi,
PevsnerFischer Meirav,
Leshkowitz Dena,
Zipori Dov
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1719
Subject(s) - mesenchymal stem cell , biology , microbiology and biotechnology , multipotent stem cell , cellular differentiation , stem cell , wnt signaling pathway , cell fate determination , downregulation and upregulation , cell , population , immunology , progenitor cell , signal transduction , genetics , transcription factor , gene , demography , sociology
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. S tem C ells 2014;32:2008–2020