Title :
Effect of hypoxia on proliferation and neural commitment of embryonic stem cells at different stages of pluripotency
Author :
Fernandes, Tiago G. ; Diogo, Maria Margarida ; Fernandes-Platzgummer, Ana ; Lobato da Silva, Claudia ; Cabral, Joaquim M. S.
Author_Institution :
Dept. of Bioeng., Inst. Super. Tecnico (IST), Lisbon, Portugal
Abstract :
We have studied the effect of low oxygen levels (2% O2), or hypoxia, in the expansion and neural commitment of mouse embryonic stem (ES) cells. When ES cells were maintained in culture with leukemia inhibitory factor (LIF), cell proliferation was reduced at low oxygen levels and a simultaneous reduction in cell viability was also observed. Morphological changes and different cell cycle patterns also occurred, suggesting some early differentiation under hypoxic conditions. However, when cells were maintained in a ground state of pluripotency, by inhibition of autocrine FGF4/ERK and GSK3 signaling, hypoxia did not affect cell proliferation, and did not induce early differentiation. Nevertheless, during neural commitment, low oxygen tension exerted a positive effect on early differentiation of ES cells, resulting in a faster commitment towards neural progenitors. Overall our results demonstrate the need to specifically regulate the oxygen content, especially hypoxia, along with other culture conditions, when developing new strategies for ES cell expansion and/or controlled differentiation.
Keywords :
cellular biophysics; diseases; ground states; neurophysiology; oxygen; ES cell expansion; O; autocrine FGF4-ERK signaling; autocrine GSK3 signaling; cell cycle patterns; cell viability; embryonic stem cell neural commitment; embryonic stem cell proliferation; hypoxia effect; leukemia inhibitory factor; low oxygen level effect; low oxygen tension; mouse embryonic stem cells; neural commitment; neural progenitors; pluripotency; pluripotency ground state; Biochemistry; Biomedical engineering; Mice; Stationary state; Stem cells; Sugar; Embryonic stem cells; expansion; hypoxia; neural commitment;
Conference_Titel :
Bioengineering (ENBENG), 2011. ENBENG 2011. 1st Portuguese Meeting in
Conference_Location :
Lisbon
Print_ISBN :
978-1-4577-0522-9
Electronic_ISBN :
978-1-4577-0521-2
DOI :
10.1109/ENBENG.2011.6026039