Are your cells holding their breath?
The hypoxic microenvironment exerts a significant influence on the epigenetic regulation of stem cell fate and behavior in vivo, and the role of low oxygen in maintenance and differentiation of stem cells in culture is coming under intense scrutiny. Epigenetic responsiveness to environmental cues in the cell environment to optimize gene expression can be modulated through chromatin or histone modification, transcriptional co-regulators and methylation/demethylation sequences (Tsai & Wu, 2014). The pathways regulating stem cell behavior are particularly interesting in the light of regenerative therapies, and oxygen level has been shown by many groups to be a master determinant of both pluripotency and differentiation. Hypoxia can, for example, induce microRNA’s that target the 3’ untranslated region of histone deacetylases, driving embryonic stem cells to differentiate into the myogenic lineage (Lee et al, 2015). Transcriptional activation of anti-angiogenesis genes during hypoxia as mediated by epigenetic changes in methylation patterns influences the status of stem cell-like populations in tumors (Ueda et al., 2014).
One of our Hypoxystation users, Brad Wouters at Princess Margaret Cancer Centre in Toronto, examines how epigenetic modifications are coordinated in response to local tumor microenvironment. His work has provided insights into the acquisition of a stem-cell phenotype in breast cancer through H3K27m3-mediated repression of the DICER promotor, reduced miRNA processing, and de-repression of ZEB1 transcription factors, resulting in hypoxia-induced EMT (Van den Beucken, 2014). Elizabeth Koch in the Toronto lab recently presented her results, obtained in the Hypoxystation, at the 14th International Wolfsberg Meeting on Molecular Radiation Biology & Oncology in Switzerland (images shown here).
Research into the epigenetic regulation of stem cell behavior and fate benefits from a more physiological culture environment as provided by an hypoxia workstation. The Hypoxystation by Don Whitley Scientific mimics those physiological conditions in a closed workstation atmosphere, tightly controlling oxygen, carbon dioxide, temperature and humidity for the duration of your cell culture. Visit us at the Cell Symposium on “Stem Cell Epigenetics” in Sitges, Spain from September 20-22 to experience the Hypoxystation for yourself. Your cells are holding their breath!
This article was written by Burga Kalz Fuller of HypOxygen
Literature on epigenetic regulation of stem cell fate at hypoxia:
Van den Beucken et al (2014) “Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER” Nature Communications 5:5203
Tsai and Wu (2014) “Epigenetic regulation of hypoxia-responsive gene expression: focusing on chromatin and DNA modifications.”Epigenetic regulation Int. J. Cancer 134, 249-256
Lee at al (2015) “MicroRNA-26a induced by hypoxia targets HDAC6 in myogenic differentiation of embryonic stem cells” Nucl. Acids Res. 43 (4): 2057-2073
Ueda et al (2014) “The Hypoxia-Inducible Epigenetic Regulators Jmjd1a and G9a Provide a Mechanistic Link between Angiogenesis and Tumor Growth” Mol. Cell Biol. 34(19): 3702-3720