A5080956707- RNA modifications and cancer
- Pregnancy and preeclampsia studies
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Genetic Syndromes and Imprinting
- Prenatal Screening and Diagnostics
- Polyamine Metabolism and Applications
University of Cambridge
2021-2023
NIHR Cambridge Biomedical Research Centre
2022
Abstract Placental function and dysfunction differ by sex but the mechanisms are unknown. Here we show that differences in polyamine metabolism associated with escape from X chromosome inactivation of gene encoding spermine synthase (SMS). Female placental trophoblasts demonstrate biallelic SMS expression, increased mRNA enzyme activity. Polyamine depletion primary reduced glycolysis oxidative phosphorylation resulting decreased acetyl-coA availability global histone hypoacetylation a...
Human trophoblast cultures provide powerful tools to model key processes of placental development. In vitro studies date have relied on commercial media that contains nonphysiological levels nutrients, and the impact these conditions metabolism function is unknown. Here, we show physiological medium (Plasmax) with nutrient metabolite concentrations recapitulating human plasma improves stem cell (hTSC) proliferation differentiation compared standard (DMEM-F12). hTSCs cultured in Plasmax-based...
The human placenta exhibits a unique genomic architecture with an unexpectedly high mutation burden and many uniquely expressed genes. aim of this study is to identify transcripts that are absent or depleted in the placenta. Here, we show 40 46 other organs have no selectively that, remaining six, liver has largest number, 26. In contrast, term 762 transcripts. Gene Ontology analysis set highlighted multiple pathways reflecting known elements placental physiology. For example, associated...
Abstract We have recently demonstrated that the human placenta exhibits a unique genomic architecture with an unexpectedly high mutation burden(Coorens et al. 2021) and it is also well recognized uniquely expresses many genes(Gong 2021). However, relatively understudied in systematic comparisons of gene expression different organs. The aim present study was to identify transcripts which were absent or depleted, comparing 46 other Here we show 40/46 organs had no selectively depleted...
Abstract Fetal sex differences play an important role in the pathophysiology of several placenta-related pregnancy complications. We previously reported that maternal circulating level a polyamine metabolite was altered fetal sex-specific manner, and associated with pre-eclampsia growth restriction. Here we show placental metabolism is these disorders polyamines influence widespread changes gene expression by regulating availability acetyl-CoA which necessary for histone acetylation. Sex are...