Single cell RNA sequencing analysis using embryonic day 9.5 placenta from control and GATA DKO mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE214389 | GEO | 2024/01/26
REPOSITORIES: GEO
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Project description:The developmental connection between the placenta and certain embryonic organs, such as the heart, is associated with normal pregnancy and complications, but how the placenta governs embryonic cardiogenesis is poorly understood. Trophoblasts fuse into a multinucleated syncytiotrophoblast (SynT) layer, primarily consisting of a placental materno-fetal interface. We identify that endogenous progesterone immunomodulatory binding factor 1 (PIBF1) is essential for trophoblast differentiation and fusion into SynT in human trophoblasts and mouse placentas. Moreover, SynT-derived PIBF1 enables the communication between SynT and adjacent vascular cells to develop the vascular network in the primary placenta and further impacts the early development of the embryonic cardiovascular system in an endocrine manner. Thus, SynT-derived factors and SynT itself in the placenta may play crucial roles in the proper organogenesis of other organs in the embryo.
2024-01-06 | GSE229265 | GEO
Project description:GATA transcription factors, particularly GATA2 and GATA3 are selectively expressed in the extraembryonic trophoblast lineage and regulates gene expression to promote trophoblast self-renewal during mammalian development. However, we have a poor understanding about the contribution of these GATA factors, in the process of syncytiotrophoblast (SynT) development. Thus, the goal of this study is to define the importance of GATA2 and GATA3 in orchestrating a global gene expression program that poises and commits mammalian trophoblast stem cells to the SynT lineage. Using the cut and run technique for GATA2 and GATA3 antibodies in the human trophoblast stem cells we are aiming to identify the direct targets of the GATA transcription factors that are essential for determining the SynT lineage. Three individual experiments were performed.
2024-01-26 | GSE214486 | GEO
Project description:The GATA transcription factors, particularly GATA2 and GATA3 are responsible for trophoblast stem cells self renewal and differentiation in mice. However, we have a poor understanding about the contribution of GATA2 and GATA3, in the trophoblast cells in humans. Thus, the goal of this study is to define the importance of GATA factors in orchestrating global gene expression program in human trophoblast stem cells. Using a RNA interference strategy (RNAi), we depleted GATA2 or GATA3 expression in human trophoblast stem cells (GATA2 KD or GATA3 KD) . We then differentiated GATA2 KD and GATA3 KD human trophoblast stem cells into syncytiotrophoblasts(SynT) and compared global gene expression patterns via RNA sequencing (RNA-seq). Three individual experiments were performed for the differentiated SynT state. The submitted files contain the data (raw fastq files, count data and deseq2 output) from those experiments.
2024-01-26 | GSE214634 | GEO
Project description:AIMS/HYPOTHESIS: Pregnancies complicated by diabetes have a higher risk of adverse outcomes for mothers and children, including predisposition to disease later in life, such as metabolic syndrome and hypertension. We hypothesized that adverse outcomes from diabetic pregnancies may be linked to compromised placental function. Our goal in this study was to identify cellular and molecular abnormalities in diabetic placenta. METHODS: Using a mouse model of diabetic pregnancy, placental gene expression was assayed at midgestation and cellular composition was analyzed at various stages. Genome-wide expression profiling was validated by quantitative PCR, and tissue localization studies were performed to identify cellular correlates of altered gene expression in diabetic placenta. RESULTS: We detected significantly altered gene expression in diabetic placenta for genes expressed in the maternal as well as those in the embryonic compartments. We also found altered cellular composition of the decidual compartment. Furthermore, the junctional and labyrinth layers were reduced in diabetic placenta, accompanied by aberrant differentiation of spongiotrophoblast cells. CONCLUSIONS/INTERPRETATION: Diabetes during pregnancy alters transcriptional profiles in the murine placenta, affecting cells of both embryonic and maternal origin, and involving several genes not previously implicated in diabetic pregnancies. The molecular changes and abnormal differentiation of multiple cell types precede impaired growth of junctional zone and labyrinth, and placenta overall. Whether these changes represent direct responses to hyperglycaemia or physiological adaptations, they are likely to play a role in pregnancy complications and outcomes, and have implications for developmental origins of adult disease. The STZ diabetic mouse model was used to investigate gene expression changes in diabetic placentae at E10.5. Placentae were dissected from 5 different FVB dams at embryonic day 10.5 under diabetic conditions and from 5 control dams. Gene expression profiles from five individual placentae from independent pregnancies per group were compared.
2011-06-01 | E-GEOD-28277 | biostudies-arrayexpress
Project description:The glycosylphosphatidylinositol (GPI) biosynthetic pathway in the endoplasmic reticulum (ER) is crucial for generating GPI-anchored proteins (GPI-APs), which are translocated to the cell surface and play a vital role in cell signaling and adhesion. This study focuses on two integral components of the GPI pathway, the PIGL and PIGF proteins, and their significance in trophoblast biology. We show that GPI pathway mutations impact on placental development impairing the development of the syncytiotrophoblast (SynT), and especially the SynT-II layer, which is essential for the establishment of the definitive nutrient exchange area within the placental labyrinth. CRISPR/Cas9 knockout of Pigl and Pigf in mouse trophoblast stem cells (mTSC) confirms the role of these GPI enzymes in syncytiotrophoblast differentiation. Mechanistically, impaired GPI-AP generation induces an excessive unfolded protein response (UPR) in the ER in mTSCs growing in stem cell conditions, akin to what is observed in human preeclampsia. Remarkably, the transcriptomic profile of Pigl- and Pigf-deficient cells separates human patient placental samples into preeclampsia and control groups suggesting an involvement of Pigl and Pigf in establishing a preeclamptic gene signature. Upon differentiation, the impairment of the GPI pathway hinders the induction of WNT signaling for early SynT-II development. Our study unveils the pivotal role of GPI biosynthesis in early placentation and uncovers a new preeclampsia gene expression profile associated with mutations in the GPI biosynthesis pathway, providing novel molecular insights into placental development with implications for enhanced patient stratification and timely interventions.
2024-05-19 | GSE266153 | GEO
Project description:The placenta serves as the structural interface for nutrient and waste exchange for proper fetal development. Although defects in placental function result in various placental disorders, molecular mechanisms orchestrating placental development and function are poorly understood. Gene targeting studies have shown that Hgf or c-Met KO embryos exhibit growth retardation and markedly smaller size of the placenta, and die by E14.5. Stem/progenitor cells in various tissues express c-Met and they participate in morphogenesis and tissue repair. Thus, we hypothesized that the HGF/c-Met signaling pathway is essential for the emergence, proliferation, and/or differentiation of putative stem/precursor cells of labyrinth trophoblasts at the midgestation stage. To examine the downstream mechanisms of HGF/c-Met signaling pathway that regulate placental labyrinth development, we performed microarray analysis and compared the transcriptional profiles of wild-type and c-Met g-KO placentas. The highly enriched gene ontology categories among the transcripts that were down-regulated in the mutant placentas were related to cell cycle, transcription, and placenta development. Surprisingly, the most highly enriched GO category among the up-regulated genes was immune response. Furthermore, genes classified as “unsaturated fatty acid metabolic process” were also significantly enriched among the up-regulated genes. This expression data suggested that HGF/c-Met signaling pathway positively regulates progression of cell cycle and transcription of placenta specific genes, and negatively regulates inflammatory reaction and fatty acids synthesis in the trophoblasts, thereby coordinating many critical cellular processes in the placenta. Freshly harvested mouse placental trophoblast was enriched for CD9 from wild -type and c-Met KO placenta with 2 independent biological replicates
2013-12-31 | E-GEOD-38342 | biostudies-arrayexpress
Project description:Healthy placental development is essential for reproductive success; failure of the feto-maternal interface results in preeclampsia and intrauterine growth retardation. We found that grainyhead-like 2 (GRHL2), a CP2-type transcription factor, is highly expressed in chorionic trophoblast cells, including basal chorionic trophoblast (BCT) cells located at the chorioallantoic interface in murine placentas. Placentas from Grhl2-deficient mouse embryos displayed defects in BCT cell polarity and basement membrane integrity at the chorioallantoic interface, as well as a severe disruption of labyrinth branchingmorphogenesis.Selective Grhl2 inactivation only in epiblastderived cells rescued all placental defects but phenocopied intraembryonic defects observed in global Grhl2 deficiency, implying the importance of Grhl2 activity in trophectoderm-derived cells. ChIPseq identified 5282 GRHL2 binding sites in placental tissue. By integrating these data with placental gene expression profiles, we identified direct and indirect Grhl2 targets and found a marked enrichment of GRHL2 binding adjacent to genes downregulated in Grhl2−/− placentas, which encoded known regulators of placental development and epithelial morphogenesis. These genes included that encoding the serine protease inhibitor Kunitz type 1 (Spint1), which regulates BCT cell integrity and labyrinth formation. In human placenta, we found that human orthologs of murine GRHL2 and its targets displayed co-regulation and were expressed in trophoblast cells in a similar domain as in mouse placenta. Our data indicate that a conserved Grhl2-coordinated gene network controls trophoblast branching morphogenesis, thereby facilitating development of the site of feto-maternal exchange. This might have implications for syndromes related to placental dysfunction. In vivo genome-wide examination of binding sites of the transcription factor GRHL2 by ChIP-seq using wild-type murine E17.5 placenta tissue. Two samples in total: one GRHL2 ChIP sample and one IgG ChIP sample using wild-type placentas tissue as antibody control.
2015-03-10 | E-GEOD-65962 | biostudies-arrayexpress
Project description:Cytotrophoblast (CTB) are bipotent progenitor epithelial cells of the human placenta, which can differentiate into invasive extravillous trophoblast (EVT) and multinucleated syncytiotrophoblast (STB). Trophoblast stem cells (TSC) have also been shown to be bipotential. In this study, we set out to probe the transcriptional diversity of first trimester CTB and compare TSC to various subgroups of CTB. We performed single-cell RNA sequencing on six normal placentae, four 6-week placentae, two of which were separated into basal and chorionic fractions prior to sequencing, and two 13-week placentae. We also sequenced three TSC lines, derived from 6-8 week placentae, to evaluate similarities and differences between primary CTB and TSC. CTB clusters displayed notable distinctions based on gestational age, with 6-week placentae showing enrichment for specific CTB subtypes, further influenced by origin from the basal or chorionic plate. Differential expression analysis of CTB from basal versus chorionic plate highlighted pathways associated with proliferation, unfolded protein response, and oxidative phosphorylation. We identified trophoblast states representing initial progenitor CTB, precursor STB, precursor and mature EVT, and multiple CTB subtypes. CTB progenitors were enriched at 6-weeks, with basal plate cells biased toward EVT, and chorionic plate cells toward STB, precursors. Clustering and trajectory inference analysis indicated that TSC were most like EVT precursor cells, with only a small percentage of TSC on the pre-STB differentiation trajectory. This was confirmed by flow cytometric analysis of 6 different TSC lines, which showed uniform expression of proximal column markers ITGA2 and ITGA5. Additionally, we found that only ITGA5+ CTB could be plated in 2D, and these cells formed only EVT upon spontaneous differentiation. Our findings suggest that distinct CTB states exist in different regions of the placenta as early as six weeks gestation and that current TSC lines most closely resemble ITGA5+ CTB, biased toward the EVT lineage.
2024-08-16 | GSE270173 | GEO
Project description:Cytotrophoblast (CTB) are bipotent progenitor epithelial cells of the human placenta, which can differentiate into invasive extravillous trophoblast (EVT) and multinucleated syncytiotrophoblast (STB). Trophoblast stem cells (TSC) have also been shown to be bipotential. In this study, we set out to probe the transcriptional diversity of first trimester CTB and compare TSC to various subgroups of CTB. We performed single-cell RNA sequencing on six normal placentae, four 6-week placentae, two of which were separated into basal and chorionic fractions prior to sequencing, and two 13-week placentae. We also sequenced three TSC lines, derived from 6-8 week placentae, to evaluate similarities and differences between primary CTB and TSC. CTB clusters displayed notable distinctions based on gestational age, with 6-week placentae showing enrichment for specific CTB subtypes, further influenced by origin from the basal or chorionic plate. Differential expression analysis of CTB from basal versus chorionic plate highlighted pathways associated with proliferation, unfolded protein response, and oxidative phosphorylation. We identified trophoblast states representing initial progenitor CTB, precursor STB, precursor and mature EVT, and multiple CTB subtypes. CTB progenitors were enriched at 6-weeks, with basal plate cells biased toward EVT, and chorionic plate cells toward STB, precursors. Clustering and trajectory inference analysis indicated that TSC were most like EVT precursor cells, with only a small percentage of TSC on the pre-STB differentiation trajectory. This was confirmed by flow cytometric analysis of 6 different TSC lines, which showed uniform expression of proximal column markers ITGA2 and ITGA5. Additionally, we found that only ITGA5+ CTB could be plated in 2D, and these cells formed only EVT upon spontaneous differentiation. Our findings suggest that distinct CTB states exist in different regions of the placenta as early as six weeks gestation and that current TSC lines most closely resemble ITGA5+ CTB, biased toward the EVT lineage.
2024-08-16 | GSE270170 | GEO
Project description:The mammalian genome contains two ERK/MAP kinase kinase genes, Map2k1 and Map2k2, encoding dual-specificity kinases responsible for ERK/MAP kinase activation. Loss of Map2k1 function in mouse causes embryonic lethality due to placental defects, while Map2k2 mutant mice survive with a normal lifespan. The Map2k1 mutation interferes with the growth of the labyrinthine region of the placenta and its vascularization. Map2k1+/-Map2k2+/- embryos also die during gestation of underdevelopment of the labyrinth. In Map2k1+/-Map2k2+/- mutants, the vascularization of the labyrinth is reduced and defects in SynT-II formation lead to the accumulation of multinucleated trophoblasts giant cells (MTG). Deletion of both Map2k1 alleles in allantoïs-derived tissues in Map2k1+/ Map2k2+/- placenta (Map2k1flox/-Map2k2+/-Tg+/Sox2Cre) increases the penetrance and the expressivity of the MTG placental phenotype. Microarray analysis with RNA extracted from placentas of E12.5 wt, Map2k1+/-Map2k2+/- and Map2k1flox/-Map2k2+/-Tg+/Sox2Cre embryos was performed to evaluate the molecular impact of the loss of Map2k alleles on placenta development. Total RNA was isolated from placentas of E12.5 Map2k1+/+Map2k2+/+(control), from E12.5 Map2k1+/-Map2k2+/- embryos (experimental) and from E12.5 and Map2k1flox/-Map2k2+/-Tg+/Sox2Cre embryos (experimental). Four specimens were analyzed per genotype.
2014-08-01 | E-GEOD-51644 | biostudies-arrayexpress