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

Daryl E. Powers, Jeffrey R. Millman, Ryan B. Huang, Clark K. Colton

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)241-254
Number of pages14
JournalBiotechnology and Bioengineering
Volume101
Issue number2
DOIs
StatePublished - Oct 1 2008

Keywords

  • Cellular energetics
  • Differentiation
  • Embryonic stem cells
  • Hypoxia
  • Oxygen
  • Proliferation

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