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Wnt/TCF7L1 transcriptional repressor axis drives primitive endoderm formation by antagonizing naive and formative pluripotency

ABSTRACT: Wnt/TCF7L1 transcriptional repressor axis drives primitive endoderm formation by antagonizing naive and formative pluripotency

PROVIDER: PRJNA718632 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14114344.fastq.gz	Fastqsanger.gz
	SRR14114345.fastq.gz	Fastqsanger.gz
	SRR14114346.fastq.gz	Fastqsanger.gz
	SRR14114347.fastq.gz	Fastqsanger.gz
	SRR14114348.fastq.gz	Fastqsanger.gz

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Wnt/TCF7L1 transcriptional repressor axis drives primitive endoderm formation by antagonizing naive and formative pluripotency

Project description:Early during preimplantation development and in heterogeneous mouse embryonic stem cells (mESC) culture, pluripotent cells are specified towards either the primed epiblast or the primitive endoderm (PE) lineage. Canonical Wnt signaling is crucial for safeguarding naive pluripotency and embryo implantation, yet the role and relevance of canonical Wnt inhibition during early mammalian development remains unknown. Here, we demonstrate that transcriptional repression exerted by Wnt/TCF7L1 promotes PE differentiation of mESCs and in preimplantation inner cell mass. Time-series RNA sequencing and promoter occupancy data reveal that TCF7L1 binds and represses genes encoding essential naive pluripotency factors and indispensable regulators of the formative pluripotency program, including Otx2 and Lef1. Consequently, TCF7L1 promotes pluripotency exit and suppresses epiblast lineage formation, thereby driving cells into PE specification. Conversely, TCF7L1 is required for PE specification as deletion of Tcf7l1 abrogates PE differentiation without restraining epiblast priming. Taken together, our study underscores the importance of transcriptional Wnt inhibition in regulating lineage specification in ESCs and preimplantation embryo development as well as identifies TCF7L1 as key regulator of this process.

2023-02-08 | GSE171204 | GEO

Chromatin immunoprecipitation of ectopic FLAG-tagged TCF7L1 followed by Mass Spectrome-try in H9-TCF7L1 Human Embryonic Stem Cells

Project description:TCF7L1 is a member of the T cell factor/Lymphoid enhancer factor (TCF/LEF) family of tran-scription factors that are part of the WNT/beta-CATENIN signaling pathway. TCF7L1 modulates transcription by interacting with other regulators on chromatin. TCF7L1 has been shown to be one of the key factors in maintaining pluripotency in human embryonic stem cells (ESCs). We previously demonstrated that the absence of TCF71 causes H9 hESCs to differentiate sponta-neously (Sierra et al., 2018 Development 145(4).pii:dev161075). Mechanistically, how TCF7L1 inhibits differentiation and keeps cells in the pluripotent state is not clear. Identifying transcrip-tional regulators on chromatin is a critical step to elucidating one of several molecular mecha-nisms controlled by TCF7L1. We previously developed a FLAG tagged TCF7L1 transgene that is controlled by a doxycycline-inducible TET-ON system and generated the H9-TCF7L1 line (Sier-ra et al., 2018 Development 145(4).pii:dev161075). Here we used the H9-TCF7L1 line and em-ployed the method called rapid immunoprecipitation (IP) mass spectrometry of endogenous pro-tein (RIME) (Mohammed et al., 2016 Nat Protoc 11(2):316-26) to identify TCF7L1-associated proteins on chromatin. Coupling of these two methods (the FLAG tagged TETON inducible sys-tem and RIME) allowed us to control the level of TCF7L1 expression in hESCs, immunopreci-pate TCF7L1 using an anti-FLAG antibody and capture TCF7L1-bound associated complexes on chromatin. Our MS analysis identified some known proteins that have been shown to associate with the WNT/beta-CATENIN/TCF/LEF pathway, as well as novel complexes that have not been linked with TCF7L1. Gene Ontology analysis suggest these proteins function in chromatin modi-fication, splicing, and RNA processing. Our data could create new ideas for in-depth studies of TCF7L1 controlling pluripotency in human ESCs and for understanding how TCF7L1 may act in other cell types.

2024-06-16 | PXD047582 | Pride

Genome-wide maps of TCF7L1 binding during early adipogenesis

Project description:Here we show through genome-wide binding studies that transcription factor 7-like 1 (TCF7L1) represses structure-related genes during adipogenesis. Intriguingly, TCF7L1 is induced in a cell contact-dependent manner by confluency in preadipocytes and is required for adipocyte differentiation by repressing transcription of cell structure genes. TCF7L1 is also sufficient to bestow adipogenic potential upon non-adipogenic cells. These results implicate TCF7L1 as a novel adipogenic competency factor that uniquely determines adipogenic fate through cell structure organization required for adipocyte gene activation. Examination of TCF7L1 binding in preadipocytes treated for 24 hours with adipogenic stimuli.

2011-09-02 | E-GEOD-31867 | biostudies-arrayexpress

Expression data from TCF7L1 Over-expression during primitive streak-like differentiation in H9 human embryonic stem cells

Project description:We used microarray analysis to profile the function of TCF7L1 in human embryonic stem cells.

2018-01-20 | GSE71668 | GEO

TCF7L1 knockdown in pancreatic cancer

Project description:RNAi mediated depletion of TCF7L1 increases activity of a Wnt-based reporter and imparts more aggressive tumor phenotypes in vitro in pancreatic cancer cell lines that express TCF7L1. We sought to determine what changes in transcription ocurred after RNAi mediated knockdown of TCF7L1 in these cells by RNA-sequencing

2017-06-20 | GSE90926 | GEO

TCF7L1 controls tuft cell differentiation

Project description:To study the functions of Tcf7l1 during gut development, we have ablated Tcf7l1 specifically in the intestinal epithelium using Shh-Cre. To determine transcriptional changes upon loss of Tcf7l1, we have isolated EpCAM-positive epithelial cells from mouse embryos using fluorescence activated cell sorting (FACS) and performed RNA-sequencing analysis.

2023-06-14 | GSE226187 | GEO

HCT116 TCF7L1 knockdown Microarray

Project description:Microarray analysis of total RNA extracted from HCT116 cells transduced with control or TCF7L1-targeted shRNA.

2017-04-25 | GSE92446 | GEO

Genome-wide maps of TCF7L1 binding during early adipogenesis

2011-09-02 | GSE31867 | GEO

Primitive endoderm stem cell lines in mice

Project description:Primitive endoderm stem cell lines in mice

| PRJNA542088 | ENA

TCF7L1 controls tuft cell differentiation

Project description:TCF7L1 controls tuft cell differentiation

| PRJNA939140 | ENA