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GATA6-AS1 Regulates GATA6 Expression to Modulate Human Endoderm Differentiation

ABSTRACT: GATA6-AS1 Regulates GATA6 Expression to Modulate Human Endoderm Differentiation

PROVIDER: PRJNA600831 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10875554_1.fastq.gz	Fastqsanger.gz
	SRR10875554_2.fastq.gz	Fastqsanger.gz
	SRR10875555_1.fastq.gz	Fastqsanger.gz
	SRR10875555_2.fastq.gz	Fastqsanger.gz
	SRR10875556_1.fastq.gz	Fastqsanger.gz

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GATA6-AS1 Regulates GATA6 Expression to Modulate Human Endoderm Differentiation

Project description:Transcriptome analysis has uncovered a series of long noncoding RNAs (lncRNAs) transcribed during cell differentiation. Here, we uncovered lncRNA GATA6-AS1 is a functional lncRNA in definitive endoderm (DE) differentiation. We found GATA6-AS1 positively regulated the expression of endoderm key factor GATA6, which was different from previous reports in other biological contexts. Further investigation showed GATA6-AS1 interacted with SMAD2/3 and recruited SMAD2/3 to the promoter region of the GATA6 gene locus. In addition, overexpression of GATA6 was able to rescue the defect of DE differentiation due to the absence of GATA6-AS1, suggesting GATA6 was the functional target of GATA6-AS1 during endoderm differentiation. Ultimately, our study uncovers GATA6-AS1 is necessary for DE and pancreas differentiation, and reveals the detailed regulation mechanism between GATA6-AS1 and DE differentiation.

2020-07-26 | GSE143499 | GEO

GATA6-AS1 Regulates GATA6 Expression to Modulate Human Endoderm Differentiation.

Project description:Transcriptome analysis has uncovered a series of long noncoding RNAs (lncRNAs) transcribed during cell differentiation, but how lncRNA is integrated with known transcriptional regulatory network is poorly understood. Here, we utilize human definitive endoderm differentiation as a model system and decipher the functional interaction between lncRNA and key transcriptional factor. We have identified GATA6-AS1, an lncRNA divergently transcribed from the GATA6 locus, is highly expressed during endoderm differentiation. Knockdown of GATA6-AS1 in human pluripotent stem cells has no influence on morphology and pluripotency; however, GATA6-AS1 depletion causes the deficiency of definitive endoderm differentiation. GATA6-AS1 positively regulates the expression of endoderm key factor GATA6. Further investigation shows GATA6-AS1 interacts with SMAD2/3 and activates the transcription of GATA6. In addition, overexpression of GATA6 is able to rescue the defect of endoderm differentiation due to the absence of GATA6-AS1, suggesting that GATA6 is the functional target of GATA6-AS1 during endoderm differentiation. Ultimately, our study reveals that GATA6-AS1 is necessary for human endoderm specification and reveals the underlying mechanism between GATA6-AS1 and GATA6.

| S-EPMC7486217 | biostudies-literature

GATA6 defines endoderm fate by controlling chromatin accessibility during differentiation of human induced pluripotent stem cells [ATAC-seq]

Project description:Investigation of the role played by GATA6 in establishing the definitive endoderm chromatin accessbility profile. We used pluripotent stem cells as a model of early development. We derived GATA6-/- pluripotent cells with an inducible GATA6 construct that permits exongenous GATA6 cDNA expression upon supplmentation of doxycycline. We differentiated GATA6 +/+ and GATA6-/- (with and without doxycyline) cells to definitive endoderm and analyzed the chromatin profile using ATAC-seq.

2021-06-07 | GSE156018 | GEO

GATA6 defines endoderm fate by controlling chromatin accessibility during differentiation of human induced pluripotent stem cells [RNA-seq]

2021-06-07 | GSE156020 | GEO

GATA6 defines endoderm fate by controlling chromatin accessibility during differentiation of human induced pluripotent stem cells [ChIP-seq]

2021-06-07 | GSE156019 | GEO

GATA6 defines endoderm fate by controlling chromatin accessibility during differentiation of human induced pluripotent stem cells [TF_ChIP-seq]

Project description:Investigation of the role played by GATA6 in establishing the definitive endoderm chromatin accessbility profile. We used pluripotent stem cells as a model of early development. We derived GATA6-/- pluripotent cells with an inducible GATA6 or FOXA2 construct that permits exongenous GATA6 or FOXA2 cDNA expression upon supplementation of doxycycline. We differentiated GATA6+/+ and GATA6-/- (with and without doxycyline) cells to definitive endoderm and analyzed transcription factor binding profiles using CHIP-seq.

2021-06-07 | GSE164231 | GEO

Global gene expression profiles of GATA6-AS1 knockdown cultures and control shRNA cultures at cardiomyocyte differentiation day 2 and day 5

Project description:Methods: RNA-seq libraries were prepared using the Illumina TruSeq technology. The libraries were quantified and samples were multiplexed in each lane of the flowcell. Cluster generation was performed and then sequenced on the Illumina HiSeq2500 system. Reads were mapped on the Human Genome Reference (GRCh38) and normalized expression table was generated. Results: At day 2, GATA6-AS1 knockdown resulted in 499 down-regulated and 1086 up-regulated differentially expressed genes (DEGs, set at -log10 p-value = 1.996; log2 changes <-1 or >1). At day 5, GATA6-AS1 knockdown resulted in 1457 down-regulated and 1166 up-regulated DEGs Conclusions: Data demonstrate GATA6-AS1 knockdown inhibits mesoderm induction and cardiomyocyte differentiation in hPSCs.

2020-09-03 | GSE157369 | GEO

Gene Expression Changes in Definitive Endoderm in response to GATA6-depletion (Affymetrix)

Project description:GATA6 is required for proper definitive endoderm formation. The mechanism of this process is poorly understood We used microarrays to identify genes whose expression is altered upon GATA6-depletion

2017-07-13 | GSE81898 | GEO

Gata6 potently initiates reprogramming of pluripotent and differentiated cells to extraembryonic endoderm stem cells [time-course microarray]

Project description:Transcription factor-mediated reprogramming is a powerful method to study cell fate changes. In this work, we demonstrate that the transcription factor Gata6 can initiate reprograming of multiple cell types to induced extraembryonic endoderm (iXEN) cells. Intriguingly, Gata6 is sufficient to drive iXEN cells from mouse pluripotent cells and differentiated neural cells. Furthermore, GATA6 induction in human ES (hES) cells also downregulates pluripotency gene expression and upregulates extraembryonic endoderm genes, revealing a conserved function in mediating this cell fate switch. Profiling transcriptional changes following Gata6 induction in mES cells reveals step-wise pluripotency factor disengagement, with initial repression of Nanog and Esrrb, then Sox2 and finally Oct4, alongside step-wise activation of extraembryonic endoderm genes. Chromatin immunoprecipitation and subsequent high-throughput sequencing analysis shows Gata6 enrichment near both pluripotency and endoderm genes, suggesting that Gata6 functions as both a direct repressor and activator. Together this demonstrates that Gata6 is a versatile and potent reprogramming factor that can act alone to drive a cell fate switch from diverse cell types. Time-course microarray analysis of Gata6-mediated reprogramming from 12 to 144 hours of doxycycline treatment in mouse embryonic stem (mES) cells compared to uninduced mES cells, embryo-derived extraembryonic endoderm (XEN) cells and Sox7 overexpressing mES cells after 144 hours of doxycycline treatment.

2015-06-30 | E-GEOD-69321 | biostudies-arrayexpress

Gata6 potently initiates reprogramming of pluripotent and differentiated cells to extraembryonic endoderm stem cells [time-course microarray]

2015-06-30 | GSE69321 | GEO