Perfluorinated Iodine Alkanes Promoted Neural Differentiation of mESCs by Targeting miRNA-34a-5p in Notch-Hes Signaling
Zhihua Ren, Tingting Ku, Yurou Gao, Xiaoxi Yang, L.Y. Meng, Qian S. Liu, Jiefeng Liang, Hanqing Xu, Chunyang Liao, Qunfang Zhou, Francesco Faiola, Guibin Jiang
Abstract
The neurodevelopmental process is highly vulnerable to environmental stress from exposure to endocrine-disrupting chemicals. Perfluorinated iodine alkanes (PFIs) possess estrogenic activities, while their potential neurodevelopmental toxicity remains blurry. In the present study, the effects of two PFIs, including dodecafluoro-1,6-diiodohexane (PFHxDI) and tridecafluorohexyl iodide (PFHxI), were investigated in the neural differentiation of the mouse embryonic stem cells (mESCs). Without influencing the cytobiological process of the mESCs, PFIs interfered the triploblastic development by increasing ectodermal differentiation, thus promoting subsequent neurogenesis. The temporal regulation of PFIs in Notch-Hes signaling through the targeting of mmu-miRNA-34a-5p provided a substantial explanation for the underlying mechanism of PFI-promoted mESC commitment to the neural lineage. The findings herein provided new knowledge on the potential neurodevelopmental toxicities of PFIs, which would help advance the health risk assessment of these kinds of emerging chemicals.