Induction of Human Pluripotent stem cells apoptosis by acute severe hypoxia is HIF1a; independent

MUCCI, SOFÍA; VERA, JONATHAN S; RODRÍGUEZ VARELA, MARÍA SOLEDAD; SEVLEVER, GUSTAVO EMILIO; MIRIUKA, SANTIAGO GABRIEL; SCASSA, MARÍA ELIDA; ROMORINI, LEONARDO

Buenos Aires

Congreso; Reunion conjunta de sociedades de biociencias; 2017

Sociedades de Biociencias

Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) are self-renewing pluripotent stem cells (PSC) that can differentiate into a wide range of specialized cells. Although moderate hypoxia (5%O2) improves PSC self-renewal, pluripotency and cell survival, we previously demonstrated that severe hypoxia (1%O2) triggers intrinsic apoptosis. HIF1α, a key hypoxia inducible transcription factor, regulates cell survival in different cellular models. In this study we explored the molecular mechanisms and HIF1α participation in PSC apoptosis induced by acute severe hypoxia. To this end, hESCs (H9 line) and hiPSCs (FN2.1 line) were cultured under physical (1%O2) or chemical acute severe hypoxia conditions. The latter was generated with CoCl2 (250µM) or dimethyl oxal glycine (1mM) treatments, which stabilize HIF-1α mimicking hypoxia. The apoptotic threshold is governed by the balance between pro- and anti-apoptotic proteins, so we measured MCL-1 (key anti-apoptotic protein in PSC) and BNIP-3 (pro-apoptotic factor regulated by hypoxia) expression levels under hypoxia.