Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ASCL1-ChiP sequence data of small cell lung cancer cell lines

ABSTRACT: Small cell lung cancer (SCLC) is known for its high metastatic potential, with most patients demonstrating clinically evident metastases in multiple organs at diagnosis. The factors contributing to this exceptional metastatic capacity have not been defined. To bridge this gap, we compared gene expression in SCLC patient samples who never experienced metastasis or relapse throughout their clinical course, versus primary SCLC patient samples from more typical patients who had metastatic disease at diagnosis. This analysis identified FOXA2 as a transcription factor strongly associated with SCLC metastasis. To clarify the contribution of ASCL1 with the interaction with FOXA2, we performed ATAC-seq on clinical FFPE samples, and PDX samples to analyze the chromatin accessibility in FOXA2+ and FOXA2- state. Furthermore, we confirmed the binding of ASCL1 by ChiP-sequence.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281524 | GEO | 2025/04/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

single-cell RNA-sequence data of clinical small cell lung cancer samples

Project description:Small cell lung cancer (SCLC) is known for its high metastatic potential, with most patients demonstrating clinically evident metastases in multiple organs at diagnosis. The factors contributing to this exceptional metastatic capacity have not been defined. To bridge this gap, we compared gene expression in SCLC patient samples who never experienced metastasis or relapse throughout their clinical course, versus primary SCLC patient samples from more typical patients who had metastatic disease at diagnosis. This analysis identified FOXA2 as a transcription factor strongly associated with SCLC metastasis. Subsequent analyses in experimental models demonstrated that FOXA2 induces a fetal neuroendocrine gene expression program and promotes multi-site metastasis. Moreover, we identified ASCL1, a transcription factor known for its initiating role in SCLC tumorigenesis, as a direct binder of the FOXA2 promoter and regulator of FOXA2 expression. Taken together, these data define the ASCL1-FOXA2 axis as a critical driver of multiorgan SCLC metastasis.

2025-04-13 | GSE281740 | GEO

FFPE-ATAC and PDX-ATAC sequence data of small cell lung cancer

Project description:Small cell lung cancer (SCLC) is known for its high metastatic potential, with most patients demonstrating clinically evident metastases in multiple organs at diagnosis. The factors contributing to this exceptional metastatic capacity have not been defined. To bridge this gap, we compared gene expression in SCLC patient samples who never experienced metastasis or relapse throughout their clinical course, versus primary SCLC patient samples from more typical patients who had metastatic disease at diagnosis. This analysis identified FOXA2 as a transcription factor strongly associated with SCLC metastasis. To clarify the contribution of ASCL1 with the interaction with FOXA2, we performed ATAC-seq on clinical FFPE samples, and PDX samples to analyze the chromatin accessibility in FOXA2+ and FOXA2- state. Furthermore, we confirmed the binding of ASCL1 by ChiP-sequence.

2025-04-13 | GSE281523 | GEO

RNA-sequence data of clinically never-metastatic primary small cell lung cancer cases and small cell lung cancer metastasis cases, FOXA2 knock-down and overexpression in cell lines

2025-04-13 | GSE281525 | GEO

ASCL1 represses a SOX9+ neural-crest-stem-like state in small cell lung cancer

Project description:ASCL1 is a neuroendocrine-lineage-specific oncogenic driver of small cell lung cancer (SCLC), highly expressed in a significant fraction of tumors. However, ~25% of human SCLC are ASCL1-low and associated with low-neuroendocrine fate and high MYC expression. Using genetically-engineered mouse models (GEMMs), we show that alterations in Rb1/Trp53/Myc in the mouse lung induce an ASCL1+ state of SCLC in multiple cells of origin. Genetic depletion of ASCL1 in MYC-driven SCLC dramatically inhibits tumor initiation and progression to the NEUROD1+ subtype of SCLC. Surprisingly, ASCL1 loss promotes a SOX9+ mesenchymal/neural-crest-stem-like state and the emergence of bone and more rarely, cartilaginous tumors. ASCL1 is critical for expression of key lineage-related transcription factors NKX2-1, FOXA2, and INSM1, and represses regulators of Hippo, Wnt and Notch developmental pathways in vivo. ASCL1 also represses SOX9 expression in human SCLC cells, suggesting a conserved function for ASCL1. Here, we utilize single-cell RNA sequencing to capture transcriptomic signatures of RPM (Rb1/Trp53/Myc), RPR2 (Rb1/Trp53/Rbl2), and RPMA (Rb1/Trp53/Myc/Ascl1) GEMM tumors to support our conclusion that in MYC-driven SCLC, ASCL1 promotes neuroendocrine fate and represses the emergence of SOX9+ non-endodermal stem-like or mesenchymal fates. These data were integrated with 4 additional invasive RPM tumors from NCBI GEO: GSE149180.

2021-05-22 | GSE169529 | GEO

Binding sites of ASCL1 and NEUROD1 in ASCL1/NEUROD1 double-positive cell lines

Project description:Small cell lung cancer (SCLC) is divided into four subtypes based on specific transcription regulators: ASCL1, NEUROD1, POU2F3, and YAP1. Around 80% of SCLC cases show neuroendocrine markers, mainly ASCL1 (called SCLC-A) or NEUROD1 (called SCLC-N). In the past, these four subtypes were thought to be completely separate. However, recent studies have shown that they can change into one another. For example, SCLC-N can develop from SCLC-A. Additionally, ASCL1 and NEUROD1 can sometimes be expressed together, although this combined subtype is not well understood. Our previous research (PMID: 35789143) showed that ASCL1 controls certain microRNAs (miRNAs), which helps keep the subtypes separate. However, the exact way NEUROD1 controls transcription in SCLC, especially when it is co-expressed with ASCL1, is still unknown. To investigate transcriptional regulation, we used Cleavage Under Targets and Tagmentation (CUT&Tag) to confirm the binding sites of ASCL1 and NEUROD1 for double positive cells.

2025-06-28 | GSE277353 | GEO

Lineage transcription factors ASCL1, NKX2-1, and PROX1 are enriched at super enhancers and co-regulate subtype-specific genes in small cell lung cancer [HiCHIP]

Project description:Heterogeneity between tumors is a major barrier to the treatment of small cell lung cancer (SCLC). Identification of molecular markers to characterize and classify tumors can facilitate the diagnosis and development of targeted therapies. Here, we analyzed genomic regions, called super enhancers (SE), across multiple SCLC cell lines and patient-derived xenograft models, and find SE enrichment is sufficient to classify SCLC models into recently defined SCLC molecular subtypes SCLC-A, SCLC-N, and SCLC-P defined by the transcription factors ASCL1, NEUROD1, and POU2F3, respectively. 3D chromatin structure analysis identified genes associated with the SE that assemble into subtype-specific tumor-signatures with genes functioning in diverse processes. Focusing on the SCLC-A subtype, transcription factors NKX2-1 and PROX1 were identified as ASCL1-interacting proteins. All three factors bind overlapping genomic regions within SEs in SCLC-A cell line models. Nevertheless, combined loss of all three factors suppresses growth of SCLC-A similar to that seen with ASCL1 loss alone, continuing to place ASCL1 as a key dependency factor in a subset of SCLC. Focusing on genes co-regulated by the three transcription factors, two SCLC-A subtype-specific cell surface proteins, SCN3A and KCNB2, were identified. Loss of either channel alone did not disrupt SCLC-A growth in vitro, but they may serve as diagnostic tools in subtyping SCLC.

2021-05-01 | GSE151001 | GEO

Lineage transcription factors ASCL1, NKX2-1, and PROX1 are enriched at super enhancers and co-regulate subtype-specific genes in small cell lung cancer [RNA-seq]

2021-05-01 | GSE151000 | GEO

Lineage transcription factors ASCL1, NKX2-1, and PROX1 are enriched at super enhancers and co-regulate subtype-specific genes in small cell lung cancer [ChIP-seq]

2021-05-01 | GSE150999 | 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

Distinct Function for ASCL1 and NEUROD1 in Pulmonary Neuroendocrine Tumors (RNA-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 RNA-seq analysis performed on two ASCL1high and two NEUROD1high human SCLC cell lines to identify gene expression patterns in these cells. Also, we performed RNA-seq in mouse neuroendocrine lung tumors obtained from Trp53;Rb1;Rbl2 triple knockout model mice treated with Adeno-CMVCRE intratracheally.

2016-07-21 | E-GEOD-69393 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data