RRC ID 81810
Author Sarma SN, Nagano R, Ohsako S.
Title Tyroxine Hydroxylase-Positive Neuronal Cell Population is Increased by Temporal Dioxin Exposure at Early Stage of Differentiation from Human Embryonic Stem Cells.
Journal Int J Mol Sci
Abstract BACKGROUND:The neurological effects of short-term dioxin exposure during the fetal period is an important health risk in humans. Here, we investigated the effects of dioxin on neural differentiation using human embryonic stem cells (hESCs) to evaluate human susceptibility to dioxin.
METHODS:Using an enzymatic bulk passage, neural differentiation from human ESCs was carried out. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was added to various stages of culture. The expression levels of the neuronal markers microtubule-associated protein 2 (MAP2) and thyroxine hydroxylase (TH) were measured by RT-qPCR and image analysis of immunostaining.
RESULTS:Although early-stage neuronal cells are quite resistant to TCDD, the numbers of neural rosettes and increases in mRNA expression levels and the number of cells positive for MAP2 and TH were significant by temporal exposure at embryoid body stage (Day9-exposure group). In contrast, the TCDD exposures against ESCs (Day0-exposure group) and differentiated neural cells (Day35-exposure group) were not affected at all. The increment was similarly observed by continuous exposure of TCDD from Day9 through Day60.
CONCLUSIONS:These results indicated that dioxin exposure during the early stage of differentiation from hESCs increases the contents of neuronal cells, especially TH-positive neuronal cells. Regulations of aryl hydrocarbon receptor (AHR) signaling in an early stage of embryogenesis should be investigated extensively to understand the mechanism underlying the increase in neuronal cell populations and to apply the knowledge to regenerative medicine.
Volume 20(11)
Published 2019-5-31
DOI 10.3390/ijms20112687
PII ijms20112687
PMID 31159217
PMC PMC6600215
MeSH Animals Biomarkers Cell Differentiation / drug effects* Cells, Cultured Dioxins / pharmacology* Dopaminergic Neurons / cytology Dopaminergic Neurons / drug effects Dopaminergic Neurons / metabolism Fluorescent Antibody Technique Gene Expression Genes, Reporter Human Embryonic Stem Cells / cytology* Human Embryonic Stem Cells / drug effects Human Embryonic Stem Cells / metabolism* Humans Mice Neurons / cytology* Neurons / drug effects Neurons / metabolism* Polychlorinated Dibenzodioxins / pharmacology RNA, Messenger / genetics Rats Time Factors Tyrosine 3-Monooxygenase / metabolism*
IF 4.556
Resource
Human and Animal Cells Hep G2(RCB1886) SK-N-SH(RCB0426) PC-12(RCB0009)