Effects of oxygen on mouse embryonic stem cell growth, phenotype retention, and cellular energetics

Most embryonic stem (ES) cell research is performed with a gas phase oxygen partial pressure (pO₂) of 142 mmHg, whereas embryonic cells in early development are exposed to pO₂ values of 0-30 mmHg. To understand effects of these differences, we studied murine ES (mES) growth, maintenance of stem cell...

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Veröffentlicht in:Biotechnology and bioengineering 2008-10, Vol.101 (2), p.241-254
Hauptverfasser: Powers, Daryl E, Millman, Jeffrey R, Huang, Ryan B, Colton, Clark K
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Sprache:eng
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Zusammenfassung:Most embryonic stem (ES) cell research is performed with a gas phase oxygen partial pressure (pO₂) of 142 mmHg, whereas embryonic cells in early development are exposed to pO₂ values of 0-30 mmHg. To understand effects of these differences, we studied murine ES (mES) growth, maintenance of stem cell phenotype, and cell energetics over a pO₂ range of 0-285 mmHg, in the presence or absence of differentiation-suppressing leukemia inhibitory factor (LIF). With LIF, growth rate was sensitive to pO₂ but constant with time, and expression of self-renewal transcription factors decreased at extremes of pO₂. Subtle morphological changes suggested some early differentiation, but cells retained the ability to differentiate into derivatives of all three germ layers at low pO₂. Without LIF, growth rate decreased with time, and self-renewal transcription factor mRNA decreased further. Gross morphological changes occurred, and overt differentiation occurred at all pO₂. These findings suggested that hypoxia in the presence of LIF promoted limited early differentiation. ES cells survived oxygen starvation with negligible cell death by increasing anaerobic metabolism within 48 h of anoxic exposure. Decreasing pO₂ to 36 mmHg or lower decreased oxygen consumption rate and increased lactate production rate. The fraction of ATP generated aerobically was 60% at or above 142 mmHg and decreased to 0% under anoxia, but the total ATP production rate remained nearly constant at all pO₂. In conclusion, undifferentiated ES cells adapt their energy metabolism to proliferate at all pO₂ between 0 and 285 mmHg. Oxygen has minimal effects on undifferentiated cell growth and phenotype, but may exert more substantial effects under differentiating conditions. Biotechnol. Bioeng. 2008;101: 241-254.
ISSN:0006-3592
1097-0290
DOI:10.1002/bit.21986