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Folic Acid Exposure Rescues Spina Bifida Aperta Phenotypes in Human Induced Pluripotent Stem Cell Model.
- Source :
-
Scientific reports [Sci Rep] 2018 Feb 13; Vol. 8 (1), pp. 2942. Date of Electronic Publication: 2018 Feb 13. - Publication Year :
- 2018
-
Abstract
- Neural tube defects (NTDs) are severe congenital abnormalities, caused by failed closure of neural tube during early embryonic development. Periconceptional folic acid (FA) supplementation greatly reduces the risk of NTDs. However, the molecular mechanisms behind NTDs and the preventive role of FA remain unclear. Here, we use human induced pluripotent stem cells (iPSCs) derived from fetuses with spina bifida aperta (SBA) to study the pathophysiology of NTDs and explore the effects of FA exposure. We report that FA exposure in SBA model is necessary for the proper formation and maturation of neural tube structures and robust differentiation of mesodermal derivatives. Additionally, we show that the folate antagonist methotrexate dramatically affects the formation of neural tube structures and FA partially reverts this aberrant phenotype. In conclusion, we present a novel model for human NTDs and provide evidence that it is a powerful tool to investigate the molecular mechanisms underlying NTDs, test drugs for therapeutic approaches.
- Subjects :
- Cell Differentiation drug effects
Down-Regulation drug effects
Humans
Induced Pluripotent Stem Cells cytology
Induced Pluripotent Stem Cells metabolism
Muscle Development drug effects
Neurons cytology
Neurons drug effects
PAX3 Transcription Factor genetics
PAX7 Transcription Factor genetics
Spheroids, Cellular cytology
Spheroids, Cellular drug effects
Up-Regulation drug effects
Folic Acid pharmacology
Induced Pluripotent Stem Cells drug effects
Phenotype
Spina Bifida Cystica pathology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 8
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 29440666
- Full Text :
- https://doi.org/10.1038/s41598-018-21103-8