31 May

Karlijn studied the processes causing mutation accumulation in healthy stem cells during early embryogenesis and fetal development. In this thesis, we found that fetal stem cells show a higher mutation rate compared to adult stem cells of the same tissue type, which is caused by processes active in all cell types. This increased mutation rate might contribute to the higher incidence of certain types of cancer, such as leukemia, during childhood. To further elaborate on this, we catalogued mutation accumulation in stem cells of Down syndrome fetuses, because these children have a higher risk do develop childhood leukemia. Indeed, we found an elevated mutation load in these cells. Pluripotent stem cells of the early embryo hold great promise for regenerative medicine because they have the capacity to differentiate to any somatic cell type. We showed that these cells in hypoxic cell culture have a comparable mutation rate as their isogenic embryonic cells during embryogenesis, indicating that these cells in culture are more stable as previously thought. Additionally, we showed that chemotherapy exposure causes an increased mutation load in fetal stem cells and activation of regular stress pathways.

The entire thesis can be found here: https://dspace.library.uu.nl/handle/1874/416883

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