Journal
STEM CELL RESEARCH
Volume 14, Issue 3, Pages 356-368Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.scr.2015.02.007
Keywords
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Funding
- National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [2011-0019352]
- Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A120262]
- National Research Foundation of Korea [2011-0019352] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Mesenchymal stromal cells (MSCs) have been extensively utilized for various cell therapeutic trials, but the signals regulating their stromal function remain largely unclear. Here, we show that canonical Wnt signals distinctively regulate MSCs in a biphasic manner depending on signal intensity, i.e., MSCs exhibit proliferation and progenitor self-renewal under low Wnt/beta-catenin signaling, whereas they exhibit enhanced osteogenic differentiation with priming to osteoblast-like lineages under high Wnt/beta-catenin signaling. Moreover, low or high levels of beta-catenin in MSCs distinctly regulated the hematopoietic support of MSCs to promote proliferation or the undifferentiated state of hematopoietic progenitors, respectively. A gene expression study demonstrated that different intracellular levels of beta-catenin in MSCs induce distinct transcriptomic changes in subsets of genes belonging to different gene function categories. Different beta-catenin levels also induced differences in intracellular levels of the beta-catenin co-factors, Tcf-1 and Lef-1. Moreover, nano-scale mass spectrometry of proteins that co-precipitated with beta-catenin revealed distinctive spectra of proteins selectively interacting with beta-catenin at specific expression levels. Together, these results show that Wnt/beta-catenin signals can coax distinct transcription milieu to induce different transcription profiles in MSCs depending on the signal intensity and that fine-tuning of the canonical Wnt signaling intensity can regulate the phase-specific functionality of MSCs. (C) 2015 The Authors. Published by Elsevier B.V.
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