aalto1 untyped-item.component.html
Continuous hypoxic culturing of human embryonic stem cells enhances Ssea-3 and Myc levels
Loading...
Access rights
openAccess
publishedVersion
URL
Journal Title
Journal ISSN
Volume Title
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
This publication is imported from Aalto University research portal.
View publication in the Research portal (opens in new window)
View/Open full text file from the Research portal (opens in new window)
Other link related to publication (opens in new window)
View publication in the Research portal (opens in new window)
View/Open full text file from the Research portal (opens in new window)
Other link related to publication (opens in new window)
Unless otherwise stated, all rights belong to the author. You may download, display and print this publication for Your own personal use. Commercial use is prohibited.
Date
Department
Major/Subject
Mcode
Degree programme
Language
en
Pages
Series
PloS One, Volume 8, issue 11, pp. 1-10
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% O2). 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 HIF2α, but not HIF1α. 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.
Description
VK: symmys
Keywords
Other note
Citation
Närvä, E, Pursiheimo, J-P, Laiho, A, Rahkonen, N, Reddy Emani, M, Viitala, M, Laurila, K, Sahla, R, Lund, R, Lähdesmäki, H, Jaakkola, P & Lahesmaa, R 2014, 'Continuous hypoxic culturing of human embryonic stem cells enhances Ssea-3 and Myc levels', PloS One, vol. 8, no. 11, e78847, pp. 1-10. https://doi.org/10.1371/journal.pone.0078847