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Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation [Cut&Run]

ABSTRACT: To investigate the regulation of human enteroendocrine cell differentiation, we established Neurog3ER inducible cell lines. We then analyzed ASCL1 and NEUROD1 binding using data obtained from CUT&RUN of at 96h.

ORGANISM(S): Homo sapiens

PROVIDER: GSE238272 | GEO | 2024/01/11

REPOSITORIES: GEO

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Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation

Project description:Enteroendocrine cells (EECs) secrete serotonin (enterochromaffin [EC] cells) or specific peptide hormones (non-EC cells) that serve vital metabolic functions. The basis for terminal EEC diversity remains obscure. By forcing activity of the transcription factor (TF) NEUROG3 in 2D cultures of human intestinal stem cells, we replicated physiologic EEC differentiation and examined transcriptional and cis-regulatory dynamics that culminate in discrete cell types. Abundant EEC precursors expressed stage-specific genes and TFs. Before expressing pre-terminal NEUROD1, post-mitotic precursors oscillated between transcriptionally distinct ASCL1+ and HES6hi cell states. Loss of either factor accelerated EEC differentiation substantially and disrupted EEC individuality; ASCL1 or NEUROD1 deficiency had opposing consequences on EC and non-EC cell features. These TFs mainly bind cis-elements that are accessible in undifferentiated stem cells, and they tailor subsequent expression of TF combinations that underlie discrete EEC identities. Thus, early TF oscillations retard EEC maturation to enable accurate diversity within a medically important cell lineage.

2024-01-10 | GSE238276 | GEO

Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation [ChIP-seq]

Project description:To investigate the regulation of human enteroendocrine cell differentiation, we established Neurog3ER inducible cell lines. We then analysed active histone marks using data obtained from H3K27ac ChIP-seq at various time points.

2024-01-11 | GSE238271 | GEO

Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation [Multiome-seq]

Project description:To investigate the regulation of human enteroendocrine cell differentiation, we established Neurog3ER inducible cell lines. We then performed simultaneous gene expression profiling and chromatin analysis at single cell level using data obtained from Multiome-seq at various time points.

2024-01-11 | GSE238275 | GEO

Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation [scRNA-seq]

Project description:To investigate the regulation of human enteroendocrine cell differentiation, we established Neurog3ER inducible cell lines. We then performed gene expression profiling analysis at single cell level using data obtained from single cell RNA-seq of at various time points.

2024-01-11 | GSE238274 | GEO

Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation [bulk ATAC-seq]

Project description:To investigate the regulation of human enteroendocrine cell differentiation, we established Neurog3ER inducible cell lines. We then performed chromatin analysis using data obtained from ATAC-seq of 2 independent human lines at various time points.

2024-01-11 | GSE238269 | GEO

Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation [bulk RNA-seq]

Project description:To investigate the regulation of human enteroendocrine cell differentiation, we established Neurog3ER inducible cell lines. We then performed gene expression profiling analysis using data obtained from RNA-seq of 2 independent human lines at various time points.

2024-01-11 | GSE238270 | GEO

Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation [Cut&Run]

Project description:Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation [Cut&Run]

| PRJNA998713 | ENA

Mouse duodenal enteroendocrine transcriptome

Project description:Using genetically modifed mice to express fluorescent reporter in proglucagon expressing cells (GluVenus) or in all enteroendocrine cells (NeuroD1), we purifed positive and negative cells by FACS from duodenal epithelial cells and identified transcripts enriched in positive populations

2018-12-31 | GSE114913 | GEO

Cut & Run-seq analysis for transcription factors overexpression in GI-MEN cells

Project description:Cut & Run analysis was performed in an neuroblastoma cell line to analyze DNA bindings of ASCL1-tag-HA in GI-MEN ASCL1-tag-HA cells and GI-MEN ASCL1-tag-HA+4TFs cells; analyze DNA bindings of MYCN, PHOX2B and H3K27ac in, GI-MEN 4TFs cells, and GI-MEN ASCL1-tag-HA+4TFs cells.

2023-11-21 | GSE214793 | GEO

Distinct Function for ASCL1 and NEUROD1 in Pulmonary Neuroendocrine Tumors (ChIP-seq)

Project description:Small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are high-grade pulmonary neuroendocrine tumors. The neural basic helix-loop-helix (bHLH) transcription factors ASCL1 and NEUROD1 have been shown to play crucial roles in promoting the malignant behavior and survival of human SCLC cell lines. In this study, we find ASCL1 and NEUROD1 identify distinct neuroendocrine tumors, bind distinct genomic loci, and regulate mostly distinct genes. ASCL1 and NEUROD1 are often bound in super-enhancers that are associated with highly expressed genes in their respective SCLC cell lines suggesting different cell lineage of origin for these tumors. ASCL1 targets oncogenic genes such as MYCL1, RET, and NFIB, while NEUROD1 targets the oncogenic gene MYC. Although ASCL1 and NEUROD1 regulate different genes, many of these gene targets commonly contribute to neuroendocrine and cell migration function. ASCL1 in particular also regulates genes in the NOTCH pathway and genes important in cell-cycle dynamics. Finally, we demonstrate ASCL1 but not NEUROD1 is required for SCLC and LCNEC tumor formation in current in vivo genetic mouse models of pulmonary neuroendocrine tumors ChIP-seq analysis performed on three ASCL1high and two NEUROD1high human SCLC cell lines to identify ASCL1 and/or NEUROD1 binding sites in these two types of cells. Also, we performed ChIP-seq for Ascl1 binding sites in mouse neuroendocrine lung tumors obtained from Trp53;Rb1;Rbl2 triple knockout model mice treated with Adeno-CMVCRE intratracheally.

2016-07-21 | E-GEOD-69394 | biostudies-arrayexpress

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