Modulation of cell cycle regulator smRNA levels along human embryonic stem cells differentiation

GUILLERMO A. VIDELA RICHARDSON; MARÍA E. SCASSA; LEONARDO ROMORINI; DAMIAN D. FERNANDEZ ESPINOSA; CAROLINA BLUGUERMANN; GUSTAVO E. SEVLEVER; SANTIAGO G. MIRIUKA

Tucumán

Congreso; XLV Reunión anual de la Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular; 2009

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Human embryonic stem cells (hESC) exhibit short cell division rates and their division is controlled through unusual mechanisms of cyclin dependent kinases (CDK) regulation. hESC have extraordinary developmental plasticity, illustrated by their unlimited differentiation potential. The cyclin-CDKs complexes are master regulators of cell proliferation. These complexes phosphorylate targets such as pocket proteins (retinoblastoma, p107 and p130) that are essential for cell proliferation and are negatively regulated by small polypeptides, the CDK inhibitors (CKIs) that comprise the INK4 and the Cip/Kip families.To date, little is known about how cell cycle machinery influences hESC properties and their cell fate commitment. In this study we sought to determine the mRNAs levels of key cell cycle regulators, in both stemness and during differentiation. These factors include: CDKs, cyclins, CKIs and pocket proteins.By qRT-PCR we found that mRNA levels of both factors that inhibit proliferation (CKIs and pocket proteins) and those that promote cell division (cyclins and CDKs) are induced along hESCs differentiation. These results suggest that in hESCs cell cycle checkpoints are abbreviated or absent during stemness and established further along differentiation. We propose that these features may be required to allow the high rate of cell division necessary for early embryonic development