2. Academic Validation
  3. Primary cilium-associated genes mediate bone marrow stromal cell response to hypoxia

Primary cilium-associated genes mediate bone marrow stromal cell response to hypoxia

  • Stem Cell Res. 2014 Sep;13(2):284-99. doi: 10.1016/j.scr.2014.06.006.
James A L Brown 1,  Tapesh Santra 2,  Peter Owens 3,  Aline M Morrison 4,  Frank Barry 5
Affiliations

Affiliations

  • 1 Systems Biology Ireland, Regenerative Medicine Institute (REMEDI), National University of Ireland, Galway, Ireland; Regenerative Medicine Institute (REMEDI), National University of Ireland, Galway, Ireland. Electronic address: james.brown@nuigalway.ie.
  • 2 Systems Biology Ireland, Conway Institute, University College Dublin (UCD), Dublin, Ireland. Electronic address: tapesh.santra@gmail.com.
  • 3 Centre for Microscopy and Imaging, Anatomy Department, National University of Ireland, Galway, Ireland. Electronic address: peter.owens@nuigalway.ie.
  • 4 Regenerative Medicine Institute (REMEDI), National University of Ireland, Galway, Ireland. Electronic address: aline.morrison@nuigalway.ie.
  • 5 Systems Biology Ireland, Regenerative Medicine Institute (REMEDI), National University of Ireland, Galway, Ireland; Regenerative Medicine Institute (REMEDI), National University of Ireland, Galway, Ireland. Electronic address: frank.barry@nuigalway.ie.
PMID: 25171775 DOI: 10.1016/j.scr.2014.06.006
Abstract

Currently there is intense interest in using mesenchymal stem cells (MSC) for therapeutic interventions in many diseases and conditions. To accelerate the therapeutic use of stem cells we must understand how they sense their environment. Primary cilia are an extracellular sensory organelle present on most growth arrested cells that transduce information about the cellular environment into cells, triggering signaling cascades that have profound effects on development, cell cycle, proliferation, differentiation and migration. Migrating cells likely encounter differing oxygen tensions, therefore we investigated the effect of oxygen tension on cilia. Using bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) we found that oxygen tension significantly affected the length of cilia in primary BMSCs. Chronic exposure to hypoxia specifically down-regulated genes involved in Hedgehog signaling and re-localized the Smo and Gli2 proteins to cilia. Investigating the effects of chemotactic migration on cilia, we observed significantly longer cilia in migrating cells which was again, strongly influenced by oxygen tension. Finally, using computational modeling we identified links between migration and ciliation signaling pathways, characterizing the novel role of HSP90 and PI3K signaling in regulating BMSC cilia length. These findings enhance our current understanding of BMSC adaptions to hypoxia and advance our knowledge of BMSC biology and cilia regulation.

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