Recapitulating early human development with 8C-like cells [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA811441 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18181015_1.fastq.gz | Fastqsanger.gz | |||
| SRR18181015_2.fastq.gz | Fastqsanger.gz | |||
| SRR18181016_1.fastq.gz | Fastqsanger.gz | |||
| SRR18181016_2.fastq.gz | Fastqsanger.gz | |||
| SRR18181017_1.fastq.gz | Fastqsanger.gz |
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Project description:Recapitulating early human development with 8C-like cells
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Project description:In human embryos, major zygotic genome activation (ZGA) initiates at the eight-cell (8C) stage. Abnormal ZGA leads to developmental defects and even contributes to the failure of human blastocyst formation or implantation. However, little is known about the mechanisms regulating human ZGA, because of many challenges and constraints on research on human embryos. Here we report one type of rare 8C-like cells (8CLCs) that are discovered specifically from human preimplantation epiblast-like stem cells (prEpiSCs) and naïve embryonic stem cells. 8CLCs express a list of human ZGA genes and their transcriptome closely resemble that of the human 8C embryo. An 8C-specific reporter is further developed to isolate 8CLCs from prEpiSCs and optimize the chemical-based culture condition that increases and maintains the 8CLC population. Functionally, 8CLCs can spontaneously form blastocyst-like structures. The discovery and maintenance of 8CLCs provides an opportunity to model human ZGA and recapitulate early human development.
2022-05-27 | GSE197641 | GEO
Project description:In human embryos, major zygotic genome activation (ZGA) initiates at the eight-cell (8C) stage. Abnormal ZGA leads to developmental defects and even contributes to the failure of human blastocyst formation or implantation. However, little is known about the mechanisms regulating human ZGA, because of many challenges and constraints on research on human embryos. Here we report one type of rare 8C-like cells (8CLCs) that are discovered specifically from human preimplantation epiblast-like stem cells (prEpiSCs) and naïve embryonic stem cells. 8CLCs express a list of human ZGA genes and their transcriptome closely resemble that of the human 8C embryo. An 8C-specific reporter is further developed to isolate 8CLCs from prEpiSCs and optimize the chemical-based culture condition that increases and maintains the 8CLC population. Functionally, 8CLCs can spontaneously form blastocyst-like structures. The discovery and maintenance of 8CLCs provides an opportunity to model human ZGA and recapitulate early human development.
2022-05-27 | GSE204799 | GEO
Project description:In human embryos, major zygotic genome activation (ZGA) initiates at the eight-cell (8C) stage. Abnormal ZGA leads to developmental defects and even contributes to the failure of human blastocyst formation or implantation. However, little is known about the mechanisms regulating human ZGA, because of many challenges and constraints on research on human embryos. Here we report one type of rare 8C-like cells (8CLCs) that are discovered specifically from human preimplantation epiblast-like stem cells (prEpiSCs) and naïve embryonic stem cells. 8CLCs express a list of human ZGA genes and their transcriptome closely resemble that of the human 8C embryo. An 8C-specific reporter is further developed to isolate 8CLCs from prEpiSCs and optimize the chemical-based culture condition that increases and maintains the 8CLC population. Functionally, 8CLCs can spontaneously form blastocyst-like structures. The discovery and maintenance of 8CLCs provides an opportunity to model human ZGA and recapitulate early human development.
2022-05-27 | GSE204800 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-05-27 | GSE204801 | GEO
Project description:After fertilization, zygotic genome activation (ZGA) enables the conversion of two terminally differentiated gametes to a totipotent embryo. Zygotes further give rise to the pluripotent embryonic lineages and extraembryonic trophectoderm after the first lineage commitment. While much is learned for pluripotency regulation, how ZGA is connected to the pluripotency commitment in early embryos remains unclear. Here, we investigated the role of nuclear receptor (NR) family TFs in mouse pre-implantation embryos, whose motifs are highly enriched in accessible chromatin at the 2-cell (2C) to 8-cell (8C) stages. We found NR5A2 is required for the early development, as both knockdown and knockout of Nr5a2 led to morula arrest. 4-8C activated genes (mid-preimplantation activation), including key pluripotency marker genes (i.e. Nanog, Pou5f1, and Tdgf1) and trophectoderm genes (i.e. Klf5, Elf3, and Gata3). Genome-wide chromatin binding and RNA-seq analyses showed NR5A2 bound and regulated the 4-8C genes, including both ICM and TE genes in 2C and 8C embryos , indicating its roles in bipotency program. Interestingly, NR5A2 occupied sites predominantly reside in accessible B1 elements where its motif is embedded at the 2-8C stage. Taken together, these data demonstrate the role of NR5A2 as a key regulator that bridges ZGA to lineage segregation.
2022-12-07 | GSE218379 | GEO
Project description:Studies on gene and/or microRNA (miRNA) dysregulation in the early stages of hepatocarcinogenesis are hampered by the difficulty of diagnosing early lesions in humans. Experimental models recapitulating human hepatocellular carcinoma (HCC) are then entailed to perform this analysis. We performed miRNA and gene expression profiling to characterize the molecular events involved in the multistep process of hepatocarcinogenesis in the Resistant-Hepatocyte rat model. A high percentage of dysregulated miRNAs/genes in HCC were similarly altered in early preneoplastic lesions positive for the stem/progenitor cell marker cytokeratin-19, indicating that several HCC-associated alterations occur from the very beginning of the carcinogenic process. Our analysis also identified miRNA/gene-target networks aberrantly activated at the initial stage of hepatocarcinogenesis. Activation of the NRF2 pathway and up-regulation of the miR-200 family were among the most prominent changes. The relevance of these alterations in the development of HCC was confirmed by the observation that NRF2 silencing impaired while miR-200a overexpression promoted HCC cell proliferation in vitro. Moreover, T3-induced in vivo inhibition of the NRF2 pathway accompanied the regression of cytokeratin-19 positive nodules, suggesting that activation of this transcription factor contributes to the onset and progression of preneoplastic lesions towards malignancy. The finding that 78% of genes and 57% of dysregulated miRNAs in rat HCC have been previously associated to human HCC as well underlines the translational value of our results. Conclusions: this study indicates that most of the molecular changes found in HCC occur in the very early stages of hepatocarcinogenesis. Among these, the NRF2 pathway plays a relevant role and may represent a new therapeutic target. 20 nodules (10 weeks after initiation with DENA), 4 adenomas (10 months), 5 eHCCs (10 months) and 9 aHCCs (14 months) were dissected. 10 controls also included.
2013-02-07 | E-GEOD-44106 | biostudies-arrayexpress