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Folic Acid Exposure Rescues Spina Bifida Aperta Phenotypes in Human Induced Pluripotent Stem Cell Model

Sahakyan, V; Duelen, R; Tam, W L; Roberts, S J; Grosemans, H; Berckmans, P; Ceccarelli, G; Pelizzo, G; Broccoli, V; Deprest, J; Luyten, F P; Verfaillie, C M; Sampaolesi, M


V Sahakyan

R Duelen

W L Tam

S J Roberts

H Grosemans

P Berckmans

G Ceccarelli

G Pelizzo

V Broccoli

J Deprest

F P Luyten

C M Verfaillie

M Sampaolesi


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.


Sahakyan, V., Duelen, R., Tam, W. L., Roberts, S. J., Grosemans, H., Berckmans, P., …Sampaolesi, M. (2018). Folic Acid Exposure Rescues Spina Bifida Aperta Phenotypes in Human Induced Pluripotent Stem Cell Model. Nature, 8, 2942.

Journal Article Type Article
Acceptance Date Jan 30, 2018
Publication Date Feb 13, 2018
Deposit Date Aug 9, 2019
Publicly Available Date Aug 13, 2019
Journal Nature
Print ISSN 0028-0836
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 8
Pages 2942
Public URL


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