Modulation of cell cycle regulators mRNA levels along human embryonic stem cells differentiation

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

Hotel Catalinas Park, Tucumán, Argentina

Congreso; XLV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2009

Human embryonic stem cells (hESC) exhibit short cell divisionrates and their division is controlled through unusual mechanisms ofcyclin dependent kinases (CDK) regulation. hESC haveextraordinary developmental plasticity, illustrated by theirunlimited differentiation potential. The cyclin-CDKs complexes aremaster regulators of cell proliferation. These complexesphosphorylate targets such as pocket proteins (retinoblastoma, p107and p130) that are essential for cell proliferation and are negativelyregulated by small polypeptides, the CDK inhibitors (CKIs) thatcomprise the INK4 and the Cip/Kip families.To date, little is knownabout how cell cycle machinery influences hESC properties andtheir cell fate commitment. In this study we sought to determine themRNAs levels of key cell cycle regulators, in both stemness andduring differentiation. These factors include: CDKs, cyclins, CKIsand pocket proteins.By qRT-PCR we found that mRNA levels ofboth factors that inhibit proliferation (CKIs and pocket proteins) andthose that promote cell division (cyclins and CDKs) are inducedalong hESCs differentiation. These results suggest that in hESCscell cycle checkpoints are abbreviated or absent during stemnessand established further along differentiation. We propose that thesefeatures may be required to allow the high rate of cell divisionnecessary for early embryonic development