Biology subjects

Charalambous, M.

Publications and source records attributed to Charalambous, M..

4 recordsLinked to original sources

bioRxiv2026

IAP retrotransposons contribute to the transcriptional diversity of the murine placenta

Transposable elements (TEs) have made important contributions to the evolution of the placenta, and are argued to have played a role in the wide inter-species diversification of this critical developmental organ. Co-option of TEs by host genomes has led to the genesis of important placental genes, as well as trophoblast-specific gene regulatory elements. But whilst multiple TE subfamilies have been shown to act as transcriptional enhancers in early mouse trophoblast development, it remains unclear to what extent TEs regulate placental gene expression after the establishment of a functional fetal-maternal interface. Here, we characterised the TE regulatory and transcriptional landscape in mouse placenta and gauged their evolutionary dynamics through a comparative approach. We found that overall, the gene regulatory potential of TEs is greatly diminished in differentiated mouse trophoblast when compared to their stem cell counterpart. However, evolutionarily young intracisternal A particle (IAP) elements are highly expressed in the placenta and create several alternative, placenta-specific transcriptional start sites for protein-coding genes. IAP elements that are active in the placenta drive species-specific expression of associated genes and display wide genetic diversity between mouse strains. These putative co-option events are therefore evolutionarily recent and may represent a prime example of how TE activity can drive fast placental evolution.

genetics↗

bioRxiv2025

Placental insufficiency causes fetal growth restriction in mice lacking Delta-like homologue 1

Fetal growth restriction (FGR) affects between 3-7% of pregnancies, is associated with increased perinatal morbidity and mortality, and linked to failure of placental function. The placenta is the key transient organ in pregnancy that directs nutrient transfer, intermediary metabolism and the production of hormones that drive maternal metabolic adaptations essential for pregnancy and lactation. The exchange surface of the placenta is formed in early development by the interaction between trophoblast cells that enclose the maternal blood and extraembryonic mesodermal cells that comprise the fetal vasculature. Despite recent insights into trophoblast development derived from novel in-vitro approaches, the processes driving extraembryonic mesoderm development are not well explored. This is due to a dearth of studies employing unbiased approaches to interrogate extraembryonic mesoderm cell populations. Here we use genetic labelling techniques to separate molecular events occurring in the trophoblast from those in the mesodermal layers of the placenta. In combination with conditional targeting, we show that the imprinted gene Dlk1 is a key player in providing nutrients to the embryo by controlling the placental surface area available for nutrient exchange, and by modulating the production of placental hormones that promote maternal nutrient provision in pregnancy.

developmental biology↗

bioRxiv2023

A co-ordinated transcriptional programme in the maternal liver supplies LC-PUFAs to the conceptus using phospholipids

Essential fatty acids (EFAs) and their derivatives, the long and very long chain polyunsaturated fatty acids (LC-PUFAs), are preferentially transported by the mother to the fetus. Failure to supply EFAs is strongly linked with stillbirth, fetal growth restriction, and impaired neurodevelopmental outcomes. However, dietary supplementation during pregnancy is unable to simply reverse these outcomes, suggesting imperfectly understood interactions between dietary EFA intake and the molecular mechanisms of maternal supply. Here we combine untargeted lipidomics with transcriptional profiling of healthy and genetically-manipulated murine models to understand the maternal adaptations required to provide LC-PUFAs to the developing fetus. We discovered a late pregnancy-specific, selective activation of the Liver X Receptor signalling pathway which dramatically increases maternal supply of LC-PUFAs within circulating phospholipids. Crucially, genetic ablation of this pathway in the mother reduced LC-PUFA accumulation by the fetus. Overall our work suggests new molecular strategies for improving maternal-fetal transfer of these important lipids.

physiology↗

bioRxiv2022

Imprinted Dlk1 dosage as a size determinant of the mammalian pituitary gland

Co-regulated genes of the Imprinted Gene Network are involved in the control of growth and body size, and imprinted gene dysfunction underlies human paediatric disorders involving the endocrine system. Imprinted genes are highly expressed in the pituitary gland, among them, Dlk1, a paternally expressed gene whose membrane-bound and secreted protein products can regulate proliferation and differentiation of multiple stem cell populations. Dosage of circulating DLK1 has been previously implicated in the control of growth through unknown molecular mechanisms. Here we generate a series of mouse genetic models to modify levels of Dlk1 expression in the pituitary gland and demonstrate that the dosage of DLK1 modulates the process of stem cell commitment with lifelong impact on pituitary gland size. We establish that stem cells are a critical source of DLK1, where embryonic disruption alters proliferation in the anterior pituitary, leading to long-lasting consequences on growth hormone secretion later in life.

developmental biology↗