Abstract
We studied the effect of radiation from computed tomography (CT) scans on differentiation of human embryonic stem cells (hESCs) into neuronal lineage. hESCs were divided into three radiation exposure groups: 0-dose, low-dose, or high-dose exposure. Low dose was accomplished with a single 15 mGy CT dose index (CTDI) CT scan that approximated the dose for abdominal/pelvic CT examinations in adults while the high dose was achieved with several consecutive CT scans yielding a cumulative dose of 500 mGy CTDI. The neural induction was characterized by immunocytochemistry. Quantitative polymerase chain reaction (qPCR) and Western blots were used to measure expression of the neuronal markers PAX6 and NES and pluripotency marker OCT4. We did not find any visible morphological differences between neural precursors from irradiated and non-irradiated cells. However, quantitative analyses of neuronal markers showed that PAX6 expression was reduced following exposure to the high dose compared to 0-dose controls, while no such decrease in PAX6 expression was observed following exposure to the low dose. Similarly, a statistically significant reduction in expression of NES was observed following high-dose exposure, while after low-dose exposure, a modest but statistically significant reduction in NES expression was only observed on Day 8 of differentiation. Further studies are warranted to elucidate how lower or delayed expression of PAX6 and NES can impact human fetal brain development.
Highlights
The first few weeks of human development are considered to be the most sensitive and vulnerable to a number of teratogenic agents, including ionizing radiation [1,2]
Twenty-four hours after exposure to radiation, colonies of human embryonic stem cells (hESCs) were dissociated into single cell suspensions (Figure 1B, Day 0), and seeded into AggreWell plates with uniformly-sized wells that hold a single embryoid body (EB) (Figure 1B, Day 1)
These EBs were already stained positive for a neural precursor marker, PAX6, and a neural differentiation marker, nestin, in both non-irradiated and irradiated samples (Figure 2)
Summary
The first few weeks of human development are considered to be the most sensitive and vulnerable to a number of teratogenic agents, including ionizing radiation [1,2]. Other work using human neural progenitor cells (NPCs) has shown altered neural development and gene expression following chronic γ-ray exposure [7] These authors reported that 496 mGy of γ-irradiation delivered over a duration of 72 h can affect neuronal differentiation, whereas altered gene expression was observed at a dose lower than 100 mGy. These authors reported that 496 mGy of γ-irradiation delivered over a duration of 72 h can affect neuronal differentiation, whereas altered gene expression was observed at a dose lower than 100 mGy Another group using in vitro models studied the responsiveness of hESCs, derived neural stem cells (NSCs), and mature neurons to high-dose ionizing radiation [14].
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