Centrioles account for centrosomes and cilia formation. Recently, a link between centrosomal components and human developmental disorders has been established. However, the exact mechanisms how centrosome abnormalities influence embryogenesis and cell fate are not understood. PLK4-STIL module represents a key element of centrosome duplication cycle. We analyzed consequences of inactivation of the module for early events of embryogenesis in human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). We demonstrate that blocking of PLK4 or STIL functions leads to centrosome loss followed by both p53-dependent and -independent defects, including prolonged cell divisions, upregulation of p53, chromosome instability, and, importantly, reduction of pluripotency markers and induction of differentiation. We show that the observed loss of key stem cells properties is connected to alterations in mitotic timing and protein turnover. In sum, our data define a link between centrosome, its regulators, and the control of pluripotency and differentiation in PSCs.

Department of Histology and Embryology Masaryk University Faculty of Medicine Brno 625 00 Czech Republic

Department of Histology and Embryology Masaryk University Faculty of Medicine Brno 625 00 Czech Republic; Cellular Imaging Core Facility Central European Institute of Technology Masaryk University Brno 625 00 Czech Republic

Department of Histology and Embryology Masaryk University Faculty of Medicine Brno 625 00 Czech Republic; International Clinical Research Center St Anne's University Hospital Brno 656 91 Czech Republic

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