Identification of novel nutrient-sensitive gene regulatory networks in amniocytes from fetuses with spina bifida

Fetal spina bifida associates with dysregulation in nutrient-sensitive placental gene networks: findings from a matched case-control study

“…In further support of this theory, mothers of cases reported lower absolute intakes in vitamins B6, B12, and choline, but not folate, as well as vitamins C and D, and overall, met a lower proportion of their estimated nutrient requirements. Further, nearly half of DEGs in cases were putatively co-regulated by TFs dependent on nutrients with known links to NTDs, including and zinc 3,4 and inositol 79 , and four of the five nutrient-dependent TFs ( CAT, CTBPR2, TROVE2 , and EP300 ) predicted to regulate DEGs in cases were also identified as top TFs targeting DEGs in fetuses with NTDs in our previous study 35 . Nutrient cofactors for these TFs included zinc, vitamins B3 and B5, inositol hexaphosphate, and heme.…”

“…To determine whether patterns of differential gene expression in cases differed according to placental location, DEGs with known cell-specific expression at the maternal-fetal interface were also identified (expression threshold ≥ 1; PlacentaCellEnrich) and characterized according to known expression patterns in the placenta 32,33 . Lastly, to determine the extent to which DEGs in cases are sensitive to, or interact with, nutrients, DEGs that coded for micronutrient-dependent proteins (i.e., proteins with ≥ 1 micronutrient cofactor) were identified and used to construct DEG-nutrient interaction networks 34,35 .…”

Fetal spina bifida associates with dysregulation in nutrient‐sensitive placental gene networks: Findings from a matched case–control study

“…Here, mothers of cases reported lower absolute intakes in vitamins B6, B12, and choline, but not folate, as well as vitamins C and D, and overall, met a lower proportion of their estimated nutrient requirements 52,53 . Further, nearly half of DEGs in cases were putatively co‐regulated by TFs dependent on nutrients with known links to NTDs, including zinc 1 and inositol, 54 and four of the five nutrient‐dependent TFs ( CAT , CTBPR2 , TROVE2 , and EP300 ) predicted to regulate DEGs in cases were also identified as top TFs targeting DEGs in fetuses with NTDs in our previous study 20 . Nutrient cofactors for these TFs included zinc, vitamins B3 and B5, inositol hexaphosphate, and heme.…”

“…DEGs with known cell‐specific expression at the maternal‐fetal interface were also identified (expression threshold ≥1; PlacentaCellEnrich) and characterized according to known expression patterns in the placenta 18 . DEGs that coded for micronutrient‐dependent proteins (i.e., proteins with ≥1 micronutrient cofactor) were identified and used to construct DEG‐nutrient interaction networks 19,20 …”

“…18 DEGs that coded for micronutrientdependent proteins (i.e., proteins with ≥1 micronutrient cofactor) were identified and used to construct DEGnutrient interaction networks. 19,20 Pathway-level transcriptome analysis Gene set enrichment analysis (GSEA; version 4.2.3) was used to identify upregulated and downregulated gene sets in cases compared to PT controls and controls, following recommended methods. 21 Gene sets upregulated or downregulated in cases compared to both PT controls and controls (q < 0.05) were identified and carried forward for interpretations and visualizations.…”