miR-210 is regulated by HIF-1a; in human pluripotent stem cell cultured under hypoxic conditions

RODRÍGUEZ VARELA, MARÍA SOLEDAD; ISAJA, LUCIANA; MUCCI, SOFÍA; SEVLEVER, GUSTAVO EMILIO; SCASSA, MARÍA ELIDA; ROMORINI, LEONARDO

Mar del Plata

Congreso; LXIII Reunión anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

SAIC

Human pluripotent stem cells (hPSCs), obtained from embryos at the blastocyst stage [embryonic stem cells (hESCs)], or from reprogrammed somatic cells [human induced pluripotent stem cells (hiPSCs)] are self-renewing cells that can be differentiated into a wide range of specialized cells. hPSCs are routinely cultured under atmospheric air enriched with 5% CO2 (20% O2).However, first stages of embryogenesis evolve in a hypoxic environment. Recent evidence suggests that many stem cells are also localized in areas with, and that benefit from, low oxygen, supporting the hypothesis that hypoxia might be important for the undifferentiated phenotype. Response to low oxygen conditions is mediated primarily by gene expression changes induced by hypoxia-inducible transcriptional factors (HIFs). Prolyl-hydroxylation of HIFs at normal oxygen tension results in HIFs degradation by the proteasome. When oxygen levels drop, HIFs are no longer hydroxylated, resulting in protein accumulation.Recently several studies have shown that the expression of a specific group of microRNAs is induced under hypoxic conditions.Among them, miR-210, which is a direct transcriptional target of HIFs: HIF-1α. However, the link between hypoxia and miRNA expression in stem cells remains poorly understood and there is evidence of a HIF-1α cell type specific regulation. On this sense, we previously demonstrated that miR-210 is up-regulated by chemical and physical hypoxia in hPSCs. Due to this, we aimed to deepen our knowledge about how miR-210 is regulated in hPSCs under hypoxia and to describe some of its mRNA targets.