Project description:Single-nucleus RNA sequencing (snRNA-seq) was used to profile the transcriptome of 9,926 nuclei in opossum adult testis. This dataset includes three samples from three different individuals. This dataset is part of a larger evolutionary study of adult testis at the single-nucleus level (97,521 single-nuclei in total) across mammals including 10 representatives of the three main mammalian lineages: human, chimpanzee, bonobo, gorilla, gibbon, rhesus macaque, marmoset, mouse (placental mammals); grey short-tailed opossum (marsupials); and platypus (egg-laying monotremes). Corresponding data were generated for a bird (red junglefowl, the progenitor of domestic chicken), to be used as an evolutionary outgroup.
Project description:The placenta plays a crucial role in the normal growth and development in mammals by serving as an interface for nutrients, respiratory gases and physiological signals between the mother and fetus. Here we use a novel embryo transfer system in mice to identify the major physiological pathways in the placenta that are principally influenced by altered maternal environment. Embryos of identical genotype were transferred at the one cell stage into surrogate mothers either of the same strain or from a different strain. We analyzed the relative effects of maternal and fetal genotype on fetal weight, placental weight and the placental transcriptome at E18.5. The results show that maternal genotype overrides fetal genotype as the principal regulator of fetal weight (p<0.0001). Microarray analysis of the transcriptome in placentas revealed that a small fraction (0.25%) of placental genes are specifically regulated by maternal genotype (p<0.05, FDR<0.10). Pathway analysis of these genes using the programs Gene Ontology and MetaCore from GeneGO inc. revealed highest statistical significance in signaling pathways that regulate cell growth and lipid metabolism. These results provide a mechanistic understanding of important molecular pathways involved in maternal regulation of fetal growth and development.
Project description:The developmental origins and evolutionary histories of cell types, tissues and organ systems contribute to the ways in which their dysfunction leads to disease. In mammals for example, the nature and extent of maternal-fetal interactions, how those interactions develop, and their evolutionary history likely influence diseases of pregnancy such as infertility and preterm birth. Here we show genes that evolved to be expressed at the maternal-fetal interface in Eutherian (‘Placental') mammals play essential roles in the evolution of pregnancy and are associated with immune system disorders and preterm birth. Among these genes is the transcription factor HAND2, which suppresses estrogen signaling, an innovation of Eutherians, thereby allowing blastocyst implantation. We found that HAND2 is dynamically expressed in the decidua throughout the menstrual cycle and pregnancy, gradually decreasing to reach a low at term. HAND2 regulates a small but distinct set of target genes in endometrial stromal fibroblasts including the cytokine IL15, which was also dynamically expressed throughout the menstrual cycle and gestation, and promoted the migration of natural killer cells and extravillous cytotrophoblasts. Remarkably, we found that the HAND2 promoter loops to a distal enhancer containing SNPs implicated in the regulation of gestation length and birth weight. Collectively, these data connect HAND2 expression at the maternal-fetal interface with the evolution of implantation and gestation length regulation, and preterm birth.
Project description:The developmental origins and evolutionary histories of cell types, tissues and organ systems contribute to the ways in which their dysfunction leads to disease. In mammals for example, the nature and extent of maternal-fetal interactions, how those interactions develop, and their evolutionary history likely influence diseases of pregnancy such as infertility and preterm birth. Here we show genes that evolved to be expressed at the maternal-fetal interface in Eutherian (‘Placental') mammals play essential roles in the evolution of pregnancy and are associated with immune system disorders and preterm birth. Among these genes is the transcription factor HAND2, which suppresses estrogen signaling, an innovation of Eutherians, thereby allowing blastocyst implantation. We found that HAND2 is dynamically expressed in the decidua throughout the menstrual cycle and pregnancy, gradually decreasing to reach a low at term. HAND2 regulates a small but distinct set of target genes in endometrial stromal fibroblasts including the cytokine IL15, which was also dynamically expressed throughout the menstrual cycle and gestation, and promoted the migration of natural killer cells and extravillous cytotrophoblasts. Remarkably, we found that the HAND2 promoter loops to a distal enhancer containing SNPs implicated in the regulation of gestation length and birth weight. Collectively, these data connect HAND2 expression at the maternal-fetal interface with the evolution of implantation and gestation length regulation, and preterm birth.
Project description:The chorio-decidual interface (CDi) is formed by chorion trophoblasts (CTCs) and immune cell-rich decidua (DECs) cells. The roles of human leukocyte antigen (HLA)-G and progesterone receptor membrane component 2 (PGRMC2) in mediating innate immune homeostasis at this maternal-fetal interface interface were investigated.
Project description:Immunological tolerance towards the semi-allogeneic fetus is one of many maternal adaptations required for a successful pregnancy. T cells are major players of the adaptive immune system and balance tolerance and protection at the maternal-fetal interface, however, their repertoire and subset programming is still poorly understood. Utilizing emerging scRNA-seq technologies we simultaneously obtained transcript, limited protein, and receptor repertoire at the single-cell level, from decidual and matched maternal peripheral T cells. In agreement with previous work, we find that the decidua maintains a tissue-specific distribution of T cells compared to the periphery. We find that decidual T cells maintain a unique transcriptome programming, characterized by restraint of inflammatory pathways by overexpression of negative regulators. Furthermore, we show little clonal overlap between the decidua and periphery, suggesting minimal ongoing traffic between these scites. Overall, our data demonstrate the power of multi-omic analysis in revealing regulation of fetal-maternal immune co-existence.
Project description:Monodelphis domestica develops ex utero. Here, we have investigated the changes in the transcriptomics of adipose tissue during juvenile development to get further insights into the reprograming in marsupial mammals.
Project description:Recently, microRNAs (miRNAs) have emerged as new players in the fine tuning of embryo development and implantation in mammals via posttranscriptional gene regulation mechanisms. Applying custom made multispecies arrays we aimed to analyze expression profile of microRNAs in peri-implantation porcine conceptuses/trophoblasts to identify their potential role at the maternal-fetal interface during the critical period of maternal recognition of pregnancy and implantation.