ROSCOVITINE, A SMALL PURINE-LIKE CDK INHIBITOR, TRIGGERS APOPTOSIS IN HUMAN EMBRYONIC STEM CELLS

GUILLERMO A. VIDELA RICHARDSON; GUSTAVO E SEVLEVER; CAROLINA P GARCIA; SANTIAGO G. MIRIUKA; VERONICA ALEJANDRA FURMENTO; LEONARDO ROMORINI; MARIA E SCASSA

San Francisco

Congreso; ISSCR 14th ANNUAL MEETING; 2016

Human embryonic stem cells (hESCs) are derived from the inner cell mass of the blastocyst, during a stage of development defined by rapid cell division rates. These cells possess the unique characteristic of indefinite self-renewal while retaining an undifferentiated state. Protein kinase complexes formed by the association of cyclins and their catalytic subunits called cyclin dependent kinases (CDKs) represent the key molecules that orderly regulate progression through the cell cycle. In hESCs, elevated cyclin activity combined with lack of endogenous CDK inhibitors results in increased activity of CDK1 and CDK2 and consequently in diminished G1 and G2 cell cycle phases. Acute inhibition of CDK1 or CDK2 in proliferating somatic cells generally results in reversible arrest of the cell cycle without significant cell death. However, in other cellular contexts, CDK inhibitors could induce cell differentiation or apoptosis. Therefore, CDKs have cell-type specific functions, and compensatory roles exist among different CDK isoforms, which in turn could play pivotal roles in the regulation of proliferation and apoptosis. Herein, we used Roscovitine (ROSC), a small purine-like CDK inhibitor, to examine the role of CDK1 and CDK2 inhibition in WA09 hESC line.