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Reduced fatty acid synthesis and enhanced oxidation promote human definitive endoderm differentiation by mediating SMAD3 nuclear localization via acetylation

ABSTRACT: Reduced fatty acid synthesis and enhanced oxidation promote human definitive endoderm differentiation by mediating SMAD3 nuclear localization via acetylation

PROVIDER: PRJNA901872 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22298019_1.fastq.gz	Fastqsanger.gz
	SRR22298019_2.fastq.gz	Fastqsanger.gz
	SRR22298020_1.fastq.gz	Fastqsanger.gz
	SRR22298020_2.fastq.gz	Fastqsanger.gz
	SRR22298021_1.fastq.gz	Fastqsanger.gz

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Reduced fatty acid synthesis and enhanced oxidation promote human definitive endoderm differentiation by mediating SMAD3 nuclear localization via acetylation

Project description:Metabolic remodeling is one of the earliest events that occur during the early differentiation of embryonic stem cells (ESCs), but how these metabolic changes are regulated and participate in the cell differentiation is still largely undissected. Here, we define the fatty acid metabolism as a key player in definitive endoderm (DE) differentiation from human ESCs. During DE differentiation, lipogenesis is decreased while fatty acid β oxidation is enhanced. This dynamic is due to the phosphorylation of lipogenic enzyme acetyl-CoA carboxylase (ACC), which is mediated by AMP-activated protein kinase (AMPK) and inhibits the de novo fatty acid synthesis. More importantly, inhibition of fatty acid synthesis by either its inhibitors or AMPK agonist, significantly promotes the human endoderm differentiation, while blockade of the fatty acid oxidation by genetic manipulation or chemical antagonists impairs the differentiation. The de novo fatty acid synthesis inhibition and fatty acid β oxidation maintaining contribute to the accumulation of cellular acetyl-CoA, which is the essential substrate for protein acetylation. Further study reveals that SMAD3 acetylation and the subsequent subcellular localization exhibit significant change upon interfering fatty acid metabolism. Mechanistically, the accumulation of cellular acetyl-CoA guarantees the acetylation of key transcription factor SMAD3, which further causes the nuclear localization and activation of SMAD signaling pathway to promote DE differentiation. Thus, our current study reveals a fatty acid synthesis/oxidation shift during early differentiation and presents an instructive role of fatty acid metabolism in regulating human early endoderm differentiation.

2023-07-02 | GSE217992 | GEO

Reduced fatty acid synthesis and enhanced oxidation promote human definitive endoderm differentiation

2023-07-02 | GSE218319 | GEO

Saracatinib Promotes Definitive Endoderm Differentiation by Inhibition of FAK-YAP Signaling Axis

Project description:Optimizing the efficiency of definitive endoderm differentiation is significant for the generation of diverse organ-like structures. In this study, we utilized saracatinib to enhance definitive endoderm differentiation in pluripotent stem cells. We found saracatinib significantly improved the definitive endoderm differentiation at low concentrations. To investigate the impact of 0.5 μM saracatinib on definitive endoderm differentiation of ESC H1 cells, we conducted RNA-seq analysis with differentiated cells with or without 0.5 μM saracatinib treatment.

2023-12-24 | GSE251992 | GEO

A distinct microRNA signature for definitive endoderm derived from human embryonic stem cells

Project description:This SuperSeries is composed of the following subset Series: GSE16678: MicroRNA expression data from differentiation of human Cyt49 ESCs into definitive endoderm in feeder-free conditions GSE16681: mRNA expression data from differentiation of human ESCs into definitive endoderm, Cyt49 on matrigel GSE16687: MicroRNA expression data from differentiation of human Cyt49 ESCs into definitive endoderm on MEF feeder layers GSE16689: MicroRNA expression data from differentiation of human H9 ESCs into definitive endoderm on MEF feeder layers Refer to individual Series

2010-07-30 | E-GEOD-16690 | biostudies-arrayexpress

Project description:Eomes related gene regulation in Definitive Endoderm

| PRJNA369195 | ENA

mRNA expression data from differentiation of human ESCs into definitive endoderm, Cyt49 on matrigel

Project description:hESCs can differentiate into the three primary embryonic lineages (endoderm, mesoderm, ectoderm) as well as extraembryonic tissues. Definitive endoderm (DE) is the first step into the pathway to endoderm derived tissues: pancreas, liver, gut, lung. We used microarrays to detail the changes in mRNA expression during the transition from pluripotent hESCs into definitive endoderm.

2010-07-30 | GSE16681 | GEO

Project description:Precisely co-ordinated activation of lineage specific transcription factors direct cell fate decisions during mouse early development. The T-box transcription factor Eomes is dynamically expressed during mouse gastrulation and is a key regulator of the anterior visceral endoderm (AVE), cardiac mesoderm and definitive endoderm (DE) lineages. The cis-acting regulatory elements that direct spatiotemporally restricted Eomes expression domains have yet to be elucidated. To understand transcriptional regulation of Eomes in Definitive Endoderm open chromatin data was generated by ATAC-seq and histone modifications identified by ChIP-seq. Interactions at the Eomes locus and the loci of two related transcription factors Foxa2 and Lhx1, was also determined by NG Capture-C.

2017-01-30 | GSE94048 | GEO

2017-01-30 | GSE94249 | GEO

Transcriptional remodeling by OTX2 directs specification and patterning of mammalian definitive endoderm [ATAC-seq]

Project description:We discovered a role for the transcription factor OTX2 in formation of mouse definitive endoderm (DE). We used ATAC-seq to identify open chromatin regions in OTX2-depleted definitive endoderm cells and identify sites with changed accessibility during DE differentiation

2024-06-26 | GSE254431 | GEO

MicroRNA expression data from differentiation of human H9 ESCs into definitive endoderm on MEF feeder layers

Project description:Pluripotent hESCs can differentiate into the three primary embryonic lineages (endoderm, mesoderm, ectoderm) as well as extraembryonic tissues. Definitive endoderm (DE) is the first step into the pathway to endoderm dreived tissues (pancreas, liver, gut, lung). We used microarrays to detail the changes in microRNA expression during the transition from pluripotent hESCs into definitive endoderm.

2010-07-30 | GSE16689 | GEO

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