Počet záznamů: 1

Human Embryonic Stem Cells Suffer from Centrosomal Amplification

  1. 1.
    0367964 - UEM-P 2012 RIV US eng J - Článek v odborném periodiku
    Holubcová, Z. - Matula, P. - Sedláčková, M. - Vinarský, Vladimír - Doležalová, Dáša - Bárta, Tomáš - Dvořák, Petr - Hampl, Aleš
    Human Embryonic Stem Cells Suffer from Centrosomal Amplification.
    Stem Cells. Roč. 29, č. 1 (2011), s. 46-56 ISSN 1066-5099
    Grant CEP: GA ČR GA204/09/2044
    Grant ostatní:GA MŠk(CZ) 1M0538; GA MŠk(CZ) 2B06052; EU FP6 project ESTOOLS(XE) LSHG-CT-2006-018739
    Program:1M
    Výzkumný záměr: CEZ:AV0Z50390703
    Klíčová slova: human embryonic stem cells * centrosome * chromosome
    Kód oboru RIV: EB - Genetika a molekulární biologie
    Impakt faktor: 7.781, rok: 2011

    Propagation of human embryonic stem cells (hESCs) in culture tends to alter karyotype, potentially limiting the prospective use of these cells in patients. The chromosomal instability of some malignancies is considered to be driven, at least in part, by centrosomal overamplification, perturbing balanced chromosome segregation. Here, we report, for the first time, that very high percentage of cultured hESCs has supernumerary centrosomes during mitosis. Supernumerary centrosomes were strictly associated with an undifferentiated hESC state and progressively disappeared on prolonged propagation in culture. Improved attachment to culture substratum and inhibition of CDK2 and Aurora A (key regulators of centrosomal metabolism) diminished the frequency of multicentrosomal mitoses. Collectively, our data indicate that supernumerary centrosomes are a significant risk factor for chromosome instability in cultured hESCs and should be evaluated when new culture conditions are being implemented.
    Trvalý link: http://hdl.handle.net/11104/0202452