Project description:Atypical protein kinase C iota (Prkci) knockout mice are embryonic lethal at gestation day 9.5 but the underlying molecular mechanisms is not known. Here , using Prkci knockout mouse model , we show that trophectoderm specific function of PKCi is essential for post-implantation mammalian development. We observed that PKCi is expressed predominantly in the trophectoderm lineage and developing placenta region in post-implantation mouse embryos. Prkci knockout or homozygous embryos show severe defect in placenta formation compared to wildtype and heterozygous embryos. Using RNA seq analysis in PKCi knockdown mouse trophoblast stem cells, we identified certain genes which are significantly upregulated upon PKCi depletion , one among them is Bone Morphogenetic protein 13 (Bmp13). Our study shows that PKCi is one of key players involved in proper development of the placenta, loss of which might be one of the reasons for early pregnancy failure.
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
Project description:Human pluripotent stem cells (hPSCs) are valuable tools for studying placental biology, yet their differentiation into bona fide trophoblast stem cells (TSCs) remains challenging. In this study, we established and thoroughly compared naive and primed-derived TSC-like cells with primary human TSCs derived from pre-implantation blastocyst and first-trimester placenta. Comprehensive analyses confirmed expression of trophoblast lineage-specific genes and typical placental features. Detailed transcriptional analyses revealed that naive-derived TSC-like cells resembled embryo and placenta-derived cell lines and differentiated faster and more directly into TSC than primed-derived cells. We used these TSC-like models to study the role of ELF5, a transcription factor indispensable for maintenance and differentiation in mouse TSC. In contrast to the mouse, knockout and knockdown experiments revealed that ELF5 is dispensable for human TSC-like cells self-renewal and differentiation. Our study provides valuable transcriptional data and highlights the utility of hPSC-derived TSC-like cells for modeling the placenta and studying gene function.