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  • 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.
  • 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. (en)
Title
  • Human Embryonic Stem Cells Suffer from Centrosomal Amplification
  • Human Embryonic Stem Cells Suffer from Centrosomal Amplification (en)
skos:prefLabel
  • Human Embryonic Stem Cells Suffer from Centrosomal Amplification
  • Human Embryonic Stem Cells Suffer from Centrosomal Amplification (en)
skos:notation
  • RIV/68378041:_____/11:00367964!RIV12-AV0-68378041
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  • P(2B06052), P(GA204/09/2044), Z(AV0Z50390703), Z(MSM0021622430)
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  • 1
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  • 202961
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  • RIV/68378041:_____/11:00367964
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  • human embryonic stem cells; centrosome; chromosome (en)
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  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [92D6BE0FDA3A]
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  • Stem Cells
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  • 29
http://linked.open...iv/tvurceVysledku
  • Dvořák, Petr
  • Hampl, Aleš
  • Bárta, Tomáš
  • Doležalová, Dáša
  • Holubcová, Z.
  • Matula, P.
  • Sedláčková, M.
  • Vinarský, Vladimír
http://linked.open...ain/vavai/riv/wos
  • 000286659300007
http://linked.open...n/vavai/riv/zamer
issn
  • 1066-5099
number of pages
http://bibframe.org/vocab/doi
  • 10.1002/stem.549
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