Multi-modal refinement of the human heart atlas during the first gestational trimester
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ABSTRACT:
PROVIDER: PRJNA1196426 | ENA |
REPOSITORIES: ENA
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Project description:Congenital heart defects are collectively frequent and a significant burden for human health. Understanding the developmental origins of such anomalies in the first and longest-lived vital organ is key to improving diagnoses, prognoses and therapies. However, although the atlas of human cardiac cells before birth continues to benefit from increased sampling, equivalencies across different investigators’ datasets or with animal models remain tenuous. We have determined the individual transcriptomes of nearly fifty thousand human heart cells from three fetuses between post-conceptional weeks (pcw) 8-11, and enriched their initial identification with a spatial transcriptomics analysis of six slices from two stage-matched samples. Integrations across modalities, sex and time points both internally and with earlier atlases have revealed the existence of previously unidentified, transient contractile, conductive and stromal cell types and their likely lineage relationships during the first trimester. Further analyses at varying levels of spatiotemporal resolution enabled us to validate charactistics of these cardiac cells in dozens of other samples and across a wide range of cell population sizes and ages. This resource advances knowledge about cell-autonomous states and adds precision to the repertory of contextual influences, including tissular and positional, exerted by and on the diverse lineages of the developing human heart during a critical time window.
2025-01-01 | GSE283967 | GEO
Project description:Human first trimester villous cytotrophoblast: 8-10 gestational week vs. 12-14 gestational week
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Project description:The study compares expression differences between first and second trimester placenta in humans. RNA-Sequencing was performed on villi obtained at 7-8 (n=8) and 13-14 (n=6) weeks’ gestational age.
2021-06-02 | E-MTAB-9203 | biostudies-arrayexpress
Project description:Human placenta bulk mRNA-sequencing from n=124 first trimester (59 female, 65 male) and n=43 third trimester (18 female, 25 male) tissue samples. A subset of 23 pregnancies has matched placenta tissue collected at both first and third trimester. Tissue was collected at Cedars-Sinai Medical Center in Los Angeles, California, USA. First trimester placenta was collected at gestational ages of 70-100 days from leftover tissue from chorionic villus sampling for prenatal genetic diagnosis, after cleaning to remove maternal decidua. Third trimester placenta was collected after delivery at gestational ages 254-290 days from the fetal side near the umbilical cord insertion site beneath the amnion. Tissue was stored in RNAlater RNA Stabilization Solution (Invitrogen) at -80C until further processing. All pregnancies were conceived without fertility treatments, were normal karyotype, and resulted in live singleton births. Mothers with pre-existing diabetes or hypertension were excluded from the study, but not excluded if complications developed during pregnancy, though most pregnancies were uncomplicated. The average parental age was advanced (over 35 years old) but principal components analysis did not show clustering by either maternal or paternal age. RNA extraction was performed with physical homogenization of tissue followed by the AllPrep DNA/RNA/miRNA Universal Kit (QIAGEN), then 1 ug of the total RNA elution was used for library construction using the Illumina TruSeq Stranded mRNA library preparation kit (Illumina), with polyA mRNA selection then cDNA synthesis using SuperScript II reverse transcriptase (Invitrogen) and random primers. The cDNA was converted into double stranded DNA and PCR-amplified, then purified with Agencourt AMPure XP beads (Beckman Coulter). Sample libraries were multiplexed and sequenced on a NovaSeq 6000 platform (Illumina) using 75bp single-end mRNA-sequencing, with average 30 million reads per sample. Differential expression analysis was performed with DEseq2 to compare first versus third trimester placenta, adjusted for fetal sex [PubMed ID: 38271627]. Subanalyses were also performed to identify sex differences.
2024-01-31 | GSE247382 | GEO
Project description:Physiological oxygen tension rises dramatically in the placenta between 8 and 14 weeks of gestation. Abnormalities in this period can lead to gestational diseases, whose underlying mechanisms remain unclear. We explored the changes at mRNA level by comparing the transcriptomes of human placentas at 8-10 gestational weeks and 12-14 gestational weeks. A total of 20 samples were collected and divided equally into four groups based on sex and age. Cytotrophoblasts were isolated and sequenced using RNAseq. Key genes were identified using two different methods: DESeq2 and weighted gene co-expression network analysis (WGCNA). We also constructed a local database of known targets of hypoxia-inducible factor (HIF) subunits, alpha and beta, to investigate expression patterns likely linked with changes in oxygen. Patterns of gene enrichment in and among the four groups were analyzed based on annotations of gene ontology (GO) and KEGG pathways. We characterized the similarities and differences between the enrichment patterns revealed by the two methods and the two conditions (age and sex), as well as those associated with HIF targets. Our results provide a broad perspective of the processes that are active in cytotrophoblasts during the rise in physiological oxygen, which should benefit efforts to discover possible drug-targeted genes or pathways in the human placenta.
2021-03-15 | GSE163023 | GEO
Project description:To characterize the human plasma microtranscriptome profile at first trimester of pregnancy in presence or not of pregnancy complications, we sequenced microRNAs in plasma samples collected from pregnant women between the 4th and the 16th weeks of pregnancy. We then performed differential expression analyses to assess the miRNA profile diffrences according to the presence of pregnancy complications or not (i.e. Gestational diabetes mellitus, Gestational hypertension or preeclampsia vs. normal pregnancies).
2022-10-24 | GSE216275 | GEO
Project description:To characterize the human plasma microtranscriptome profile at first trimester of pregnancy in presence or not of pregnancy complications, we sequenced microRNAs in plasma samples collected from pregnant women between the 6th and the 15th weeks of pregnancy as a replication cohort. We then performed differential expression analyses to assess the miRNA profile diffrences according to the presence of pregnancy complications or not (i.e. Gestational diabetes mellitus, Gestational hypertension or preeclampsia vs. normal pregnancies).
2022-11-03 | GSE216997 | GEO
Project description:To investigate the role of miRNA in the placental development, we analyzed miRNA expression profiles in the first and third trimester human placentas. Total RNA was isolated from 12 placentas (6 from first trimester and 6 from third trimester). miRNA expression profiles were determined by Affymetrix GeneChip 2.0 miRNA Microarray.
2012-12-14 | GSE42915 | GEO
Project description:We used a whole genome approach to identify major functional gene categories (including xenobiotic transporters and metabolizing enzymes) whose expression depends on gestational age. STUDY DESIGN: We compared gene expression profiles of 1st (45-59 days) and 2nd trimester (109-115 days), and C-section term placentae. RESULTS: In 1st trimester placentae, genes related to cell cycle, DNA, aminoacids and carbohydrate metabolism were significantly overrepresented, while genes related to signal transduction were downregulated. In the organism defense category, we identified genes involved in chemical response, metabolism, and transport. Analysis of signal transduction pathways suggested, and subsequently confirmed independently, that the Wnt pathway was regulated by gestational age. CONCLUSIONS: Our study will serve as a reference database to gain insight into the regulation of gene expression in the developing placentae and, thus, allow comparisons with placentae from complicated pregnancies such as those in women experiencing gestational diabetes, pre-eclampsia and teratogenic sequelae. Experiment Overall Design: Comparison of plaental gene expression profiles of three gestational stages (1st trimester (45-59 days), 2nd trimester (109-115 days), and C-section term placentae), with four replicates each,
2008-06-17 | E-GEOD-9984 | biostudies-arrayexpress
Project description:To investigate the role of miRNA in the placental development, we analyzed miRNA expression profiles in the first and third trimester human placentas. Total RNA was isolated from 12 placentas (6 from first trimester and 6 from third trimester). miRNA expression profiles were determined by Affymetrix GeneChip 2.0 miRNA Microarray. Using miRNA microarray to determine miRNA expression profiles in the human placenta between first and third trimester pregnancies.
2012-12-14 | E-GEOD-42915 | biostudies-arrayexpress