Publications by authors named "Lehua Chen"
Folic acid (FA) is well known to prevent neural tube defects (NTDs), but we do not know why many human NTD cases still remain refractory to FA supplementation. Here, we investigate how the DNA demethylase TET1 interacts with maternal FA status to regulate mouse embryonic brain development. We determined that cranial NTDs display higher penetrance in non-inbred than in inbred Tet1 embryos and are resistant to FA supplementation across strains.
View Article and Find Full Text PDFThe etiology of neural tube defects (NTDs) involves complex gene-environmental interactions. Folic acid (FA) prevents NTDs, but the mechanisms remain poorly understood and at least 30% of human NTDs resist the beneficial effects of FA supplementation. Here, we identify the DNA demethylase TET1 as a nexus of folate-dependent one-carbon metabolism and genetic risk factors post-neural tube closure.
View Article and Find Full Text PDFArticle Synopsis
- - Gastrulation initiates with the formation of the primitive streak in the epiblast, where TET1 plays key roles in gene activation and repression during cell lineage decisions, particularly in mouse embryonic stem cells (ESCs).
- - The study shows that TET1 regulates the balance between neuroectoderm and mesoderm/endoderm fates; TET1 targeted the Wnt repressor Tcf7l1 to suppress Wnt/β-catenin and Nodal signaling pathways during this process.
- - TET1's functions vary based on genomic context and developmental stages, as it cooperates with Polycomb to repress certain genes and later shifts to repress Wnt signaling, while some hypermethylated genes