Chromosome Instability in Stem Cells

Rebuzzini, Paola; Zuccotti, Maurizio; Redi, Carlo Alberto; Garagna, Silvia

doi:10.1002/9781118647110.ch3

Cited by 1 publication

(2 citation statements)

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“…Chromosomal alterations were analyzed 24 h and 4 days after irradiation in MP and EP cells using multicolor Figure 3 shows typical karyograms of a normal and an aberrant cell. No aneuploidy (eg, trisomy as reported by reference [10] or [14]) was observed in any of the samples analyzed. The fraction of tetraploid cells did not exceed 2% and was not correlated to the radiation treatment (Table 1).…”

Section: Chromosomal Aberrationsmentioning

confidence: 82%

“…These somewhat contradicting findings may not only stem from variations in the radiation type and dosage but also from the quality of the ES cells used. Indeed, the usage of hES cells comes with a caveat as suboptimal or prolonged culture can lead to genomic variations [10] altering the stem cell properties and differentiation capabilities. For example, enzymatic passaging techniques such as trypsin passage were reported to be associated with abnormalities of chromosomes 12 and 17 in hES cells [11], while others did not detect differences in the genomic stability of hES cells when comparing mechanical with collagenase IV based dissociation methods [12].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ionizing Radiation Alters Human Embryonic Stem Cell Properties and Differentiation Capacity by Diminishing the Expression of Activin Receptors

Luft

Arrizabalaga

Kulish

et al. 2017

Stem Cells and Development

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Exposure of the embryo to ionizing radiation (IR) is detrimental as it can cause genotoxic stress leading to immediate and latent consequences such as functional defects, malformations, or cancer. Human embryonic stem (hES) cells can mimic the preimplantation embryo and help to assess the biological effects of IR during early development. In this study, we describe the alterations H9 hES cells exhibit after X-ray irradiation in respect to cell cycle progression, apoptosis, genomic stability, stem cell signaling, and their capacity to differentiate into definitive endoderm. Early postirradiation, hES cells responded with an arrest in G2/M phase, elevated apoptosis, and increased chromosomal aberrations. Significant downregulation of stem cell signaling markers of the TGF beta-, Wnt-, and Hedgehog pathways was observed. Most prominent were alterations in the expression of activin receptors. However, hES cells responded differently depending on the culture conditions chosen for maintenance. Enzymatically passaged cells were less sensitive to IR than mechanically passaged ones showing fewer apoptotic cells and fewer changes in the stem cell signaling 24 h after irradiation, but displayed higher levels of chromosomal aberrations. Even though many of the observed changes were transient, surviving hES cells, which were differentiated 4 days postirradiation, showed a lower efficiency to form definitive endoderm than their mock-irradiated counterparts. This was demonstrated by lower expression levels of SOX17 and microRNA miR-375. In conclusion, hES cells are a suitable tool for the IR risk assessment during early human development. However, careful choice of the culture methods and a vigorous monitoring of the stem cell quality are mandatory for the use of these cells. Exposure to IR influences the stem cell properties of hES cells even when immediate radiation effects are overcome. This warrants consideration in the risk assessment of radiation effects during the earliest stages of human development.

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Section: Chromosomal Aberrationsmentioning

confidence: 82%