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ALKBH5 modulates endoderm fate diversion from hESCs through the ALKBH5-GATA6-WNT/β-catenin regulatory axis.

ABSTRACT: ALKBH5 modulates endoderm fate diversion from hESCs through the ALKBH5-GATA6-WNT/β-catenin regulatory axis.

PROVIDER: PRJNA1044426 | ENA |

REPOSITORIES: ENA

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ALKBH5 modulates endoderm fate diversion from hESCs through the ALKBH5-GATA6-WNT/β-catenin regulatory axis [meRIP-seq]

Project description:N6-methyladenonsine (m6A) modification locates ubiquitously in mammalian mRNA, and profoundly impacts various physiological processes and pathogenesis. However, the precise involvement of m6A in early endoderm development has yet to be fully elucidated. Here, we reported that depletion of the m6A demethylase ALKBH5 in human embryonic stem cells (hESCs) severely impaired definitive endoderm (DE) differentiation. Within this process, ALKBH5-/- hESCs failed to undergo the primitive streak (PS) intermediate transition, which is considered as a prelude to endoderm specification. Mechanistically, we demonstrated that ALKBH5 deficiency induced m6A hypermethylation around the 3’ untranslated region (3’UTR) of GATA6 transcripts and destabilized GATA6 mRNA in a YTHDF2-dependent manner. Moreover, dysregulation of GATA6 expression ablated its occupancy with critical regulators of Wnt/β-catenin signaling pathway, thereby disrupting the signaling logic underlying DE formation. Overall, our findings unveil a mechanism whereby the ALKBH5-GATA6-WNT/β-catenin axis modulates human in vitro DE induction, and present novel insights on m6A modification in early embryonic development.

2024-10-23 | GSE248526 | GEO

ALKBH5 modulates endoderm fate diversion from hESCs through the ALKBH5-GATA6-WNT/β-catenin regulatory axis [RNA-seq]

2024-10-23 | GSE248525 | GEO

ALKBH5 modulates endoderm fate diversion from hESCs through the ALKBH5-GATA6-WNT/β-catenin regulatory axis [CUT&Tag]

2024-10-23 | GSE248527 | GEO

ALKBH5 modulates endoderm fate diversion from hESCs through the ALKBH5-GATA6-WNT/β-catenin regulatory axis [RNA-seq]

Project description:ALKBH5 modulates endoderm fate diversion from hESCs through the ALKBH5-GATA6-WNT/β-catenin regulatory axis [RNA-seq]

| PRJNA1044427 | ENA

ALKBH5 modulates endoderm fate diversion from hESCs through the ALKBH5-GATA6-WNT/β-catenin regulatory axis [CUT&Tag]

Project description:ALKBH5 modulates endoderm fate diversion from hESCs through the ALKBH5-GATA6-WNT/β-catenin regulatory axis [CUT&Tag]

| PRJNA1044428 | ENA

ALKBH5 modulates endoderm fate diversion from hESCs through the ALKBH5-GATA6-WNT/β-catenin regulatory axis [meRIP-seq]

Project description:ALKBH5 modulates endoderm fate diversion from hESCs through the ALKBH5-GATA6-WNT/β-catenin regulatory axis [meRIP-seq]

| PRJNA1044429 | ENA

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

ALKBH5 modulates endoderm fate diversion from hESCs through the ALKBH5-GATA6-WNT/β-catenin regulatory axis.

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-10-23 | GSE248528 | GEO

GATA6-AS1 Regulates GATA6 Expression to Modulate Human Endoderm Differentiation

Project description:GATA6-AS1 Regulates GATA6 Expression to Modulate Human Endoderm Differentiation

| PRJNA600831 | ENA

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

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