Project description:We detected a genome-wide differential gene enrichment between mid-trimester and term human placenta. Pathway analysis identified that cytokine-cytokine receptor interaction, NF-κB, and TNF are the leading pathways enriched in term placenta. Our analysis has provided the first-time characterization of the key players of human placental origin with molecular changes across pregnancy, which could drive human labor.
Project description:Chromatin alterations are important mediators of gene expression changes. We have recently shown that activated non-canonical NF-κB signaling (RelB/p52) recruits histone acetyltransferase CBP and deacetylase HDAC1 to selectively acetylate H3K9 (H3K9ac) to induce expression of corticotropin-releasing hormone (CRH) and prostaglandin-endoperoxide synthase-2 (PTGS2) in the human placenta. Both of these genes play a role in initiating. We performed chromatin immunoprecipitation followed by gene sequencing (ChIP-seq) in primary term human cytotrophoblast (CTB) with use of antibodies to RelB, CBP, HDAC1 and H3K9ac. We further associated these chromatin alterations with gene expression changes from mid-trimester to term in CTB by RNA sequencing (RNA-seq). We detected a genome-wide differential gene enrichment between mid-trimester and term human placenta. Pathway analysis identified that cytokine-cytokine receptor interaction, NF-κB, and TNF are the leading pathways enriched in term placenta and associated with these chromatin alterations. Our analysis has provided the first-time characterization of the key players of human placental origin with molecular changes resulting from chromatin modifications, which could drive human labor.
Project description:Microarray analysis of human fetal microglia from the mid-trimester period was performed. DEGs were identified between early and late stages of the mid-trimester gestation. Genes expressed in the human fetal microglia were also compared with mouse microglia core signature.
Project description:Human cytotrophoblast organoid cultures were established from the villous trophoblast of first trimester placentas. We analyzed the global expression profile of the cytotrophoblast organoids (CTB-ORG) and compared to the profile of the tissue of origin i.e. villous cytotrophoblast (vCTB) as well as to differentiated syncytiotrophoblast (STB) and placental fibroblasts (FIB).
Project description:Embryonic and extraembryonic development quickly diverges. Other than a globally hypomethylated genome, little is known about the epigenetic changes of placental cells throughout gestation. We profiled DNA methylation and activating/repressing histone modifications of cytotrophoblasts and four extraembryonic compartments in 2nd trimester and at term. Unexpectedly, in cytotrophoblasts, H3K9me3 occupancy precisely overlapped domains with more pronounced DNA hypomethylation and repressed transcription. At term, immunoblotting and -localization revealed extensive depletion of this and other histone modifications that paralleled increased genome-wide DNA methylation, which included hundreds of promoters. Candidate enhancers within embryonic stem cell differentially methylated regions (DMRs) revealed pluripotency factors, while those within cytotrophoblast DMRs revealed transcription factor binding motifs and genes that regulate placental development. DNA methylation, RNA, and miRNA profiling of the extraembryonic compartments identified regional specializations and gestational age regulation. Cytotrophoblast mRNAs that were down-regulated at term were enriched for genes up-regulated in severe preeclampsia. Correspondingly, immunoanalyses of cytotrophoblast histone modifications showed strong H3K27ac upregulation in severe preeclampsia. Thus, as gestation proceeded, certain cytotrophoblast histone modifications declined precipitously while, in pregnancy complications, these normal patterns were markedly perturbed. These data suggested an unusual genome-scale pattern of alterations in the abundance of histone modifications over the lifetime of the placenta. Marked alterations in this pattern were associated with pregnancy complications, indicating a possible causative role.
Project description:Trajectory modeling of first trimester placenta highlight differences between cytotrophoblast progenitors and trophoblast stem cells