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

Fundación Leloir, Buenos Aires, Argentina

Simposio; International Symposium on Stem Cell Research; 2009

Human embryonic stem cells (hESCs) are derived from the inner cell mass of the earlyembryo. hESCshold great developmental potential and are able to differentiate to all celllineages of an organism except for extraembryonic tissues, a unique property termed pluripotency.These cells exhibit high cell division rates, witha shortened G1 phase and distinctionsin molecular cell cycle regulatory parameters. As hESCs differentiate, their cellcycle structure changes dramatically so as to incorporate a significantly longer G1 phase.Moreover, their mechanism of cell cycle regulation changes to that typically seen in somaticcells. To date, little is known about how cell cycle machinery influences hESCsymmetricalself-renewal and their cell fate commitment. It is surprising that alteredlevels of several cell cycle proteins selectively affectproliferation of stem cells. Wiringof cell cycle pathways in stem cells may operate in a more rigid and non redundant fashionthan it does in other cell types. This mechanism may allow stem cells to selectivelyrespond to environmental cues by specifically up-regulating a particular component of thecell cycle engine, and to undergo self-renewal, asymmetric division, or cell differentiation.Understanding the molecular mechanisms of early patterning and cell fate allocationwill be of key importance in efforts towards inducing the directed differentiation of embryonicstem cells in research and regenerative medicine.