Human amnion epithelial cell therapy reduces hypertension-induced vascular stiffening and cognitive impairment
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE248059 | GEO | 2023/12/30
REPOSITORIES: GEO
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Project description:Background: Preeclampsia, traditionally characterized by high blood pressure and proteinuria, is a common pregnancy complication, which affects 2-8% of all pregnancies. Although children born to women with preeclampsia have a higher risk of hypertension in later life, the mechanism of this increased risk is unknown. DNA methylation is an epigenetic modification that has been studied as a mediator of cellular memory of adverse exposures in utero. Since each cell type in the body has a unique DNA profile, cell subtype composition is a major confounding factor in studies of tissues with heterogeneous cell types. The best way to avoid this confounding effect is by using purified cell types. However, the use purified cell types in large cohort translational studies is difficult. The amnion, the inner layer of the fetal membranes of placenta, is derived from the epiblast and consists of two cell types, which are easy to isolate from the delivered placenta. In this study, we demonstrate the value of using amnion samples for DNA methylation studies, revealing distinctive patterns between fetuses exposed to preeclampsia or hypertension and fetuses from normal pregnancies. Results: We performed a genome-wide DNA methylation analysis, HELP-tagging, on 62 amnion samples from placentas of uncomplicated, normal pregnancies, and those with complications of preeclampsia or hypertension. Using a regression model approach, we found 123, 85 and 99 loci with high confidence hypertension-associated, proteinuria-associated and hypertension and proteinuria-associated DNA methylation changes, respectively. We also found that these differentially methylated regions overlap loci previously reported as differentially methylated regions in preeclampsia. Conclusions: Our findings support prior observations that preeclampsia is associated with changes of DNA methylation near genes that have previously been found to be dysregulated in preeclampsia. We propose that amnionic membranes represent a valuable surrogate fetal tissue on which to perform epigenome-wide association studies of adverse intrauterine conditions.
2016-06-17 | GSE79782 | GEO
Project description:Background: Preeclampsia, traditionally characterized by high blood pressure and proteinuria, is a common pregnancy complication, which affects 2-8% of all pregnancies. Although children born to women with preeclampsia have a higher risk of hypertension in later life, the mechanism of this increased risk is unknown. DNA methylation is an epigenetic modification that has been studied as a mediator of cellular memory of adverse exposures in utero. Since each cell type in the body has a unique DNA profile, cell subtype composition is a major confounding factor in studies of tissues with heterogeneous cell types. The best way to avoid this confounding effect is by using purified cell types. However, the use purified cell types in large cohort translational studies is difficult. The amnion, the inner layer of the fetal membranes of placenta, is derived from the epiblast and consists of two cell types, which are easy to isolate from the delivered placenta. In this study, we demonstrate the value of using amnion samples for DNA methylation studies, revealing distinctive patterns between fetuses exposed to preeclampsia or hypertension and fetuses from normal pregnancies. Results: We performed a genome-wide DNA methylation analysis, HELP-tagging, on 62 amnion samples from placentas of uncomplicated, normal pregnancies, and those with complications of preeclampsia or hypertension. Using a regression model approach, we found 123, 85 and 99 loci with high confidence hypertension-associated, proteinuria-associated and hypertension and proteinuria-associated DNA methylation changes, respectively. We also found that these differentially methylated regions overlap loci previously reported as differentially methylated regions in preeclampsia. Conclusions: Our findings support prior observations that preeclampsia is associated with changes of DNA methylation near genes that have previously been found to be dysregulated in preeclampsia. We propose that amnionic membranes represent a valuable surrogate fetal tissue on which to perform epigenome-wide association studies of adverse intrauterine conditions.
2016-06-17 | GSE79781 | GEO
Project description: Not available
| S-EPMC5340142 | biostudies-literature
Project description:Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly specify somatic cell fates in cells such as pancreatic ? cells, contractile cardiomyocytes and neurons. We hypothesized that combinatorial expression of chondrocyte-specific transcription factors could directly convert human amnion cells into chondrosarcoma. Starting from a pool of candidate genes, we identified a combination of only five genes (5F pool), BCL6, T (also called BRACHYURY), c-MYC, MITF and BAF60C (also called SMARCD3) that rapidly and efficiently convert postnatal human amnion into chondrosarcoma. The cells generated expressed multiple cartilage-specific genes such as collagen type II ?1, link protein-1 and aggrecan, and exhibited characteristics of cartilage both in vivo and in vitro. Expression of the endogenous genes for T and MITF was initiated, implying that the cell conversion is due to not only the forced expression of the transgenes, but also the cellular reprogramming by the transgenes. The same set of genes converted human placental artery-derived endothelial (hPAE) cells and menstrual blood-derived cells into chondrosarcoma cells, implying that this conversion is independent of cell types. Direct conversion system from non-cartilage tissue to cartilaginous tissue contributes substantially to a major advance toward cartilage development, oncogenesis of chondrocytes, and cell-based therapy. We hypothesized that combinatorial expression of chondrocyte-specific transcription factors could directly convert human amnion cells into chondrosarcoma. Starting from a pool of candidate genes, we identified a combination of only five genes that rapidly efficiently convert postnatal human amnion into chondrosarcoma.
2011-06-07 | E-GEOD-29745 | biostudies-arrayexpress
Project description:Analysis of cultured human amnion mesenchymal cells treated with synthetic glucocorticoid dexamethasone for 48 hours. Results provide insight into the molecular response of the human amnion to glucocorticoids.
2022-09-09 | E-MTAB-9493 | biostudies-arrayexpress
Project description:Hypoxia can induce vasoconstriction followed by vascular remodeling including hypertrophy and hyperplasia of pulmonary vascular smooth muscle and proliferation of endothelial cells. The goal of this project is to elucidate the genes involved in vascular remodeling following pulmonary hypertension. Total RNA was isolated from lungs of normoxic and hypoxic treated animals. Keywords: other
2003-07-16 | GSE482 | GEO
Project description:<p>Arterial stiffening is a hallmark of early vascular aging (EVA) syndrome and an independent predictor of cardiovascular morbidity and mortality. In this case-control study we sought to identify plasma metabolites associated with EVA syndrome in the setting of hypertension. An untargeted metabolomic approach was used to identify plasma metabolites in an age-, BMI- and sex-matched groups of EVA (n = 79) and non-EVA (n = 73) individuals with hypertension. After raw data processing and filtration, 497 putative compounds were characterized, out of which 4 were identified as lysophosphaditylcholines (LPCs) [LPC (18:2), LPC (16:0), LPC (18:0) and LPC (18:1)]. A main finding of this study shows that identified LPCs were independently associated with EVA status. Although LPCs have been shown previously to be positively associated with inflammation and atherosclerosis, we observed that hypertensive individuals characterized by 4 down-regulated LPCs had 3.8 times higher risk of EVA compared to those with higher LPC levels (OR = 3.8, 95% CI 1.7 – 8.5, P < .001). Our results provide new insights into a metabolomic phenotype of vascular aging and warrants further investigation of negative association of LPCs with EVA status. This study suggests that LPCs are potential candidates to be considered for further evaluation and validation as predictors of EVA in patients with hypertension </p>
2020-01-14 | MTBLS1359 | MetaboLights
Project description:We encapsulated common marmoset pluripotent stem cells (cmPSCs) in agarose microgels and optimised culture conditions to generate epiblast and amnion spheroids. Using this system, we investigate the effects of signalling perturbations on epiblast and amnion spheroids as a model for early lineage specification
2022-07-06 | E-MTAB-10639 | biostudies-arrayexpress
Project description:The germ cell lineage ensures reproduction, heredity and evolution. However, the mechanism for germ cell specification in primates, including humans, has been unknown. In primates, the pluripotent epiblast segregates the amnion upon implantation and thereafter initiates gastrulation to generate three germ layers. Here, we show that in cynomolgus monkeys, the SOX17/BLIMP1/TFAP2C-positive primordial germ cells (cyPGCs) arise from the dorsal amnion at embryonic day (E) 11. cyPGCs then migrate down beneath the epiblast and expand their numbers, through proliferation and continuous recruitment from the posterior amnion, around posterior yolk sac endoderm by E17. Remarkably, the amnion itself expresses BMP4, a cytokine potentially critical for PGC specification, thereby inducing cyPGCs in an autocrine fashion. Consistently, the amnion expresses T, a key mesodermal factor, prior to the onset of gastrulation. Our study demonstrates the origin of cyPGCs in the amnion, which undergoes a unique morphogenetic event prior to and independent from the gastrulation.
2016-10-12 | GSE76267 | GEO
Project description:Embryonic development is largely conserved among mammals. However, certain genes show divergent functions. By generating a transcriptional atlas containing >30,000 cells from post-implantation non-human primate embryos, we uncover that ISL1, a gene with a well-established role in cardiogenesis, controls a gene regulatory network in primate amnion. CRISPR/Cas9-targeting of ISL1 results in non-human primate embryos which do not yield viable offspring, demonstrating that ISL1 is critically required in primate embryogenesis. On a cellular level, mutant ISL1 embryos display a failure in mesoderm formation due to reduced BMP4 signaling from the amnion. Via loss of function and rescue studies in human embryonic stem cells we confirm a similar role of ISL1 in human in vitro derived amnion. This study highlights the importance of the amnion as a signaling center during primate mesoderm formation and demonstrates the potential of in vitro primate model systems to dissect the genetics of early human embryonic development.
2021-06-30 | GSE148683 | GEO