Detailed Information on Publication Record
2011
Human embryonic stem cells suffer from centrosomal amplification
HOLUBCOVÁ, Zuzana, Pavel MATULA, Miroslava SEDLÁČKOVÁ, Vladimír VINARSKÝ, Dáša DOLEŽALOVÁ et. al.Basic information
Original name
Human embryonic stem cells suffer from centrosomal amplification
Authors
HOLUBCOVÁ, Zuzana (203 Czech Republic, guarantor, belonging to the institution), Pavel MATULA (203 Czech Republic, belonging to the institution), Miroslava SEDLÁČKOVÁ (203 Czech Republic, belonging to the institution), Vladimír VINARSKÝ (203 Czech Republic, belonging to the institution), Dáša DOLEŽALOVÁ (703 Slovakia, belonging to the institution), Tomáš BÁRTA (203 Czech Republic, belonging to the institution), Petr DVOŘÁK (203 Czech Republic, belonging to the institution) and Aleš HAMPL (203 Czech Republic, belonging to the institution)
Edition
Stem Cells, 2011, 1066-5099
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
Genetics and molecular biology
Country of publisher
United States of America
Confidentiality degree
není předmětem státního či obchodního tajemství
Impact factor
Impact factor: 7.781
RIV identification code
RIV/00216224:14110/11:00051844
Organization unit
Faculty of Medicine
UT WoS
000286659300007
Keywords in English
Human embryonic stem cells; Centrosome; Chromosome; Genetic instability; CDK; Aurora A
Tags
International impact, Reviewed
Změněno: 1/8/2013 10:40, Ing. Mgr. Věra Pospíšilíková
Abstract
V originále
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. Thus, both attenuated cell attachment and deregulation of machinery controlling centrosome number contribute to centrosomal overamplification in hESCs. Linking the excessive number of centrosomes in mitoses to the ploidy indicated that both overduplication within a single cell cycle and mitotic failure contributed to generation of numerical centrosomal abnormalities in hESCs. 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.
Links
| MSM0021622430, plan (intention) |
| ||
| 2B06052, research and development project |
|