Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Recapitulating early human development with 8C-like cells [ATAC-seq]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE204800 | GEO | 2022/05/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Recapitulating early human development with 8C-like cells [ChIP-seq]

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

Recapitulating early human development with 8C-like cells [RNA-seq]

2022-05-27 | GSE197641 | GEO

NR5A2 connects genome activation to the first lineage segregation in totipotent embryos

Project description:Zygotic genome activation (ZGA) marks the beginning of the embryonic program for a totipotent embryo, which gives rise to inner cell mass (ICM), where pluripotent epiblast arises, and extraembryonic trophectoderm. While much has been learned about pluripotency regulation, how ZGA is connected to the first lineage segregation in early embryos remains elusive. Here, we investigated the role of nuclear receptor transcription factors (NR TFs), whose motifs are highly enriched in accessible chromatin at the 2-cell (2C) to 8-cell (8C) stages after ZGA. We found NR5A2, an NR TF highly induced upon ZGA, is required for early development. Genome-wide chromatin binding in 2C and 8C embryos showed NR5A2 bound cis-regulatory elements which strongly enrich B1 elements where its motif is embedded. RNA-seq showed while the zygotic genome was largely activated at the 2C stage, 4-8C-specific gene activation was substantially impaired in Nr5a2 KD embryos. At the 8C stage, NR5A2 preferentially regulated its targets including a subset of early ICM genes. Consistently, NR5A2 was required for opening 8C-specific binding sites. Interestingly, while NR5A2’s 2C-binding sites are largely closed in blastocyst, 8C-specific binding sites tend to stay open and are bound by master pluripotency TFs (NANOG, SOX2, and OCT4) in blastocyst or ESC. Further analyses showed NR5A2 regulates early ICM genes at the 8C stage, master pluripotency TFs regulate both early and late ICM genes at later stages. Taken together, these data identify NR5A2 as a key regulator in totipotent embryos that connects ZGA to the first lineage segregation in early mouse development.

2023-10-12 | GSE229740 | GEO

NR5A2 bridges zygotic genome activation to lineage segregation in early mouse development

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

Recapitulating early human development with 8C-like cells

Project description:Recapitulating early human development with 8C-like cells

| PRJNA842365 | ENA

Preimplantation mouse embryo proteome during 8C to 16C division

Project description:Preimplantation stages of mouse embryo development involve temporal and spatial specification and segregation of three late blastocyst cell lineages; trophectoderm (TE), primitive endoderm (PrE) and epiblast (EPI). Spatial separation of the outer TE lineage from the two inner-cell-mass (ICM) lineages (PrE and EPI) starts with the 8- to 16-cell transition and concludes following transit through the 16- to 32-cell stages. This results in a nascent early blastocyst ICM derived from descendants of primary founding inner cells and a secondarily contributed population; of which subsequent relative EPI versus PrE potencies are subject to debate. We showed that generation of primary but not the secondary ICM populations is highly dependent on temporally discreet activation of the mammalian target of rapamycin (mTOR – specifically mTORC1) around 8-cell stage M-phase entry. Moreover, that this role is mediated via the regulated function of the 7-methylguanosine- (7mG) cap binding initiation complex (EIF4F) and potentiating the translation of a subset of key but otherwise intransigent mRNAs containing 5’ UTR terminal oligopyrimidine (TOP-) sequence motifs. To find out translation of which mRNAs is regulated by mTOR during 8- to 16-cell transition, we analysed proteomes of control and mTOR-inhibited embryos during this time window.

2023-08-18 | PXD039423 | Pride

Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals [CUT&TAG]

Project description:Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivo and in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation (ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2-cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, and the abnormal phenotypes could be recapitulated by overexpression of H3K18R mutation and rescued by addition of Lac-CoA. By profiling the landscape of H3K18lac in human and mouse preimplantation embryos, we show that H3K18lac is enriched on the promoter regions of most major ZGA genes and corelates with their expressions. Taken together, we demonstrate the important role for lactate in major ZGA via H3K18lac, showing a conserved metabolic mechanism underlies preimplantation development of mammalian embryos.

2024-02-14 | GSE234026 | GEO

Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals [RNA-seq]

2024-02-14 | GSE234025 | GEO

Recapitulating early human development with 8C-like cells [RNA-seq]

Project description:Recapitulating early human development with 8C-like cells [RNA-seq]

| PRJNA811441 | ENA

Recapitulating early human development with 8C-like cells [ATAC-seq]

Project description:Recapitulating early human development with 8C-like cells [ATAC-seq]

| PRJNA842369 | ENA