Human Embryonic Stem Cells Suffer from Centrosomal Amplification

0367964 - ÚEM 2012 RIV US eng J - Journal Article
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. E-ISSN 1549-4918
R&D Projects: GA ČR GA204/09/2044
Grant - others:GA MŠk(CZ) 1M0538; GA MŠk(CZ) 2B06052; EU FP6 project ESTOOLS(XE) LSHG-CT-2006-018739
Program: 1M
Institutional research plan: CEZ:AV0Z50390703
Keywords : human embryonic stem cells * centrosome * chromosome
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 7.781, year: 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.
Permanent Link: http://hdl.handle.net/11104/0202452