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Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation.

ABSTRACT: Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation.

PROVIDER: PRJNA955079 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24152410_1.fastq.gz	Fastqsanger.gz
	SRR24152410_2.fastq.gz	Fastqsanger.gz
	SRR24152411_1.fastq.gz	Fastqsanger.gz
	SRR24152411_2.fastq.gz	Fastqsanger.gz
	SRR24152412_1.fastq.gz	Fastqsanger.gz

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Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation [screen]

Project description:Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation [screen]

| PRJNA955098 | ENA

Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation [screen]

Project description:Enteroendocrine cells (EECs) are hormone-producing cells residing in the epithelium of stomach, small intestine (SI) and colon. EECs regulate various aspects of metabolic activity including insulin levels, satiety, gastrointestinal secretion and motility. The generation of different EEC lineages of the SI is incompletely understood. We now report a TFome-wide CRISPR knockout screen in adult human intestinal organoids to identify dominant transcription factors controlling EEC differentiation. ZNF800 is discovered as a master repressor for endocrine lineage commitment, which particularly restricts enterochromaffin cell differentiation by directly controlling an endocrine TF network centered on PAX4. Thus, organoid models allow unbiased functional SCRISPR screens for genes that program cell differentiation.

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Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation [CHIP-seq]

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Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation [scRNA-seq]

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Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation [scRNA-seq]

Project description:Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation [scRNA-seq]

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Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation [CHIP-seq]

Project description:Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation [CHIP-seq]

| PRJNA955099 | ENA

Unbiased transcription factor CRISPR screen identifies ZNF800 as master repressor of enteroendocrine differentiation.

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

2023-10-26 | GSE229586 | GEO

Identification of functional enteroendocrine regulators by real-time single-cell differentiation mapping

Project description:Homeostatic regulation of the intestinal enteroendocrine lineage hierarchy is a poorly understood process. We resolved transcriptional changes during enteroendocrine differentiation in real-time at single-cell level using a novel knock-in allele of Neurog3, the master regulator gene briefly expressed at the onset of enteroendocrine specification. A bi-fluorescent reporter, Neurog3Chrono, measures time from the onset of enteroendocrine differentiation and enables precise positioning of single-cell transcriptomes along an absolute time axis. This approach yielded a definitive description of the enteroendocrine hierarchy and its sub-lineages, uncovered differential kinetics between sub-lineages, and revealed time-dependent hormonal plasticity in enterochromaffin and L-cells. The time-resolved map of transcriptional changes predicted multiple novel molecular regulators. Nine of these were validated by conditional knockout in mice or CRISPR-modification in intestinal organoids. Six novel candidate regulators (Sox4, Rfx6, Tox3, Myt1, Runx1t1 and Zcchc12) yielded specific enteroendocrine phenotypes. Our time-resolved single cell transcriptional map presents a rich resource to unravel enteroendocrine differentiation.

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Single cell and bulk RNA sequencing of Enteroendocrine cells from human hormone reporter organoids

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