A1 Journal article – refereed

Continuous Hypoxic Culturing of Human Embryonic Stem Cells Enhances SSEA-3 and MYC Levels




List of Authors: Narva E, Pursiheimo JP, Laiho A, Rahkonen N, Emani MR, Viitala M, Laurila K, Sahla R, Lund R, Lahdesmaki H, Jaakkola P, Lahesmaa R

Publisher: PUBLIC LIBRARY SCIENCE

Publication year: 2013

Journal: PLoS ONE

Journal name in source: PLOS ONE

Journal acronym: PLOS ONE

Number in series: 11

Volume number: 8

Issue number: 11

Number of pages: 10

ISSN: 1932-6203

DOI: http://dx.doi.org/10.1371/journal.pone.0078847


Abstract
Low oxygen tension (hypoxia) contributes critically to pluripotency of human embryonic stem cells (hESCs) by preventing spontaneous differentiation and supporting self-renewal. However, it is not well understood how hESCs respond to reduced oxygen availability and what are the molecular mechanisms maintaining pluripotency in these conditions. In this study we characterized the transcriptional and molecular responses of three hESC lines (H9, HS401 and HS360) on short (2 hours), intermediate (24 hours) and prolonged (7 days) exposure to low oxygen conditions (4% O-2). In response to prolonged hypoxia the expression of pluripotency surface marker SSEA-3 was increased. Furthermore, the genome wide gene-expression analysis revealed that a substantial proportion (12%) of all hypoxia-regulated genes in hESCs, were directly linked to the mechanisms controlling pluripotency or differentiation. Moreover, transcription of MYC oncogene was induced in response to continuous hypoxia. At the protein level MYC was stabilized through phosphorylation already in response to a short hypoxic exposure. Total MYC protein levels remained elevated throughout all the time points studied. Further, MYC protein expression in hypoxia was affected by silencing HIF2 alpha, but not HIF1 alpha. Since MYC has a crucial role in regulating pluripotency we propose that induction of sustained MYC expression in hypoxia contributes to activation of transcriptional programs critical for hESC self-renewal and maintenance of enhanced pluripotent state.


Last updated on 2021-24-06 at 10:22