Regulation of cyclin E1 expression in human pluripotent stem cells and derived neural progeny

MARIA SOLEDAD RODRIGUEZ VARELA; SOFIA MUCCI; GUILLERMO A. VIDELA RICHARDSON; MORRIS-HANON, OLIVIA; VERONICA A. FURMENTO; SANTIAGO G. MIRIUKA; GUSTAVO E. SEVLEVER; MARíA E. SCASSA; LEONARDO ROMORINI

CELL CYCLE

LANDES BIOSCIENCE

Lugar: Austin, Texas; Año: 2018

1538-4101

Humanpluripotent stem cells (hPSCs), including embryonic and induced pluripotentstem cells (hESCs and hiPSCs) show unique cell cycle characteristics, such as ashort doubling time due to an abbreviated G1 phase. Whether or not the corecell cycle machinery directly regulates the stemness and/or the differentiationpotential of hPSCs remains to be determined. To date, several scenariosdescribing the atypical cell cycle of hPSCs have been suggested, and thereforethere is still controversy over how cyclins, master regulators of the cellcycle, are expressed and regulated. Furthermore, the cell cycle profile and theexpression pattern of major cyclins in hESCs-derived neuroprogenitors (NP) havenot been studied yet. Therefore, herein we characterized the expression patternof major cyclins in hPSCs and NP. We determined that all studied cyclins mRNAexpression levels fluctuate along cell cycle. Particularly, after a thoroughanalysis of synchronized cell populations, we observed that cyclin E1 mRNAlevels increased sharply in G1/S concomitantly with cyclin E1 proteinaccumulation in hPSCs and NP. Additionally, we demonstrated that cyclin E1 mRNAexpression levels involves the activation of MEK/ERK pathway and thetranscription factors c-Myc and E2Fs in hPSCs. Lastly, our results reveal thatproteasome mediates the marked down-regulation (degradation) of cyclin E1protein observed in G2/M by a mechanism that requires a functional CDK2 but notGSK3â activity.