| Experiment Id | GSE85602 | Name | A YY1-dependent increase in aerobic metabolism is indispensable for intestinal organogenesis |
| Experiment Type | transcription profiling by array | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2024-07-11 |
| description | During late gestation, structures called villi extend into the intestinal lumen to dramatically increase the surface area of the intestinal epithelium, preparing the gut for the neonatal diet. Incomplete development of the intestine is the most common gastrointestinal complication in neonates, but the causes are unclear. We provide evidence that Yin-Yang1 (Yy1) is critical for intestinal villus development. YY1 loss in the developing endoderm had no apparent consequences until late gestation, after which the intestine differentiated poorly and exhibited severely stunted villi. Transcriptome analysis revealed that YY1 is required for mitochondrial gene expression, and ultrastructural analysis confirmed compromised mitochondrial integrity in the mutant intestine. We found increased oxidative phosphorylation gene expression at the onset of villus elongation, suggesting that aerobic respiration may function as a regulator of villus growth. Mitochondrial inhibitors blocked villus growth in a fashion similar to Yy1 loss, thus further linking oxidative phosphorylation with late-gestation intestinal development. Interestingly, we find necrotizing enterocolitis patients also exhibit decreased expression of oxidative phosphorylation genes. Our study highlights the still unappreciated role of metabolic regulation during organogenesis, and suggests it may contribute to neonatal gastrointestinal disorders. Mouse embryos of the same genotypes were pooled (up to 2) to obtain 2 biological replicates of YY1f/f and Yy1f/f; Shh-Cre. Epcam positive epithelium cells were enriched using magnetic selection from Small intestines of E15.5 embryos (proximal stomach to distal caecum). Cells were then dissolved in Trizol and RNA prepared by ethanol precipitation using 10ug LPA. RNA was then processed for microarray on Affymetrix Mouse 430_2 arrays according to manufacturer's instructions. |
