Transcriptome analysis of CMT64 cells transduced with Ascl1
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE139926 | GEO | 2021/12/13
REPOSITORIES: GEO
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Project description:ASCL1 is a master transcription factor for neuroendocrine differentiation. RNA-sequencing analysis on VMRC-LCD cells following ASCL1 knockdown revealed a subset of genes possibly regulated by ASCL1.
2018-12-11 | GSE108705 | GEO
Project description:Transcriptome analysis of CMT64 cells transduced with Ascl1
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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
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
Project description:To elucidate whether or not a subtype of adenocarcinoma with neuroendocrine nature has poor prognosis, we performed gene expression profiling of an achaete-scute complex homolog 1 (ASCL1) siRNA experiment. siRNA againt ASCL1 was transfected into DMS79 cells.
2011-07-18 | E-GEOD-21216 | biostudies-arrayexpress
Project description:In castration-resistant prostate cancer, lineage plasticity mediates resistance to androgen receptor pathway inhibitors (ARPIs) and progression from adenocarcinoma to neuroendocrine prostate cancer (NEPC), a highly aggressive and poorly understood subtype. ASCL1 has emerged as a central regulator of the NEPC phenotype, driving neuroendocrine differentiation. However, ASCL1’s influence on neuronal lineage switching and maturation, as well as its partners in NEPC, remain largely unknown. Here, we provided insights into ASCL1’s cistrome reprogramming in ARPI-induced NEPC versus terminal NEPC and showed that ASCL1 binding pattern tailors the subsequent expression of transcription factor combinations that underlie discrete terminal NEPC identity. We identified FOXA2 as a major co-factor of ASCL1 in terminal NEPC that it is highly expressed in ASCL1-driven NEPC. FOXA2 and ASCL1 interact and work in concert to orchestrate terminal neuronal differentiation in prostate cancer, and regulate key neuroendocrine-associated genes including PROX1. Our findings provide insights into the molecular conduit underlying the interplay between different lineage determinant transcription factors to support the neuroendocrine identity in prostate cancer.
2024-10-23 | GSE273956 | GEO
Project description:In castration-resistant prostate cancer, lineage plasticity mediates resistance to androgen receptor pathway inhibitors (ARPIs) and progression from adenocarcinoma to neuroendocrine prostate cancer (NEPC), a highly aggressive and poorly understood subtype. ASCL1 has emerged as a central regulator of the NEPC phenotype, driving neuroendocrine differentiation. However, ASCL1’s influence on neuronal lineage switching and maturation, as well as its partners in NEPC, remain largely unknown. Here, we provided insights into ASCL1’s cistrome reprogramming in ARPI-induced NEPC versus terminal NEPC and showed that ASCL1 binding pattern tailors the subsequent expression of transcription factor combinations that underlie discrete terminal NEPC identity. We identified FOXA2 as a major co-factor of ASCL1 in terminal NEPC that it is highly expressed in ASCL1-driven NEPC. FOXA2 and ASCL1 interact and work in concert to orchestrate terminal neuronal differentiation in prostate cancer, and regulate key neuroendocrine-associated genes including PROX1. Our findings provide insights into the molecular conduit underlying the interplay between different lineage determinant transcription factors to support the neuroendocrine identity in prostate cancer.
2024-10-23 | GSE273957 | GEO
Project description:ChIP-Seq analysis performed on 5 ASCL1(+) cell lines and 2 ASCL1 (-) cell lines in order to understand the transcriptome of ASCL1 as it pertains to high-grade neuroendocrine lung cancers 5 ASCL1(+) lung cancer cell lines and 2 ASCL1(-) lung cancer cell lines were compared using ChIP-Seq analysis
2014-10-01 | E-GEOD-61197 | biostudies-arrayexpress
Project description:ASCL1, a basic helix-loop-helix family transcription factor, is a master regulator of developmental neurogenesis and a crucial component of transcription factor cocktails that can convert heterologous cell types such as fibroblasts into neurons. The ability of ASCL1 to drive neuronal differentiation is controlled by multi-site phosphorylation but how this modification controls the genome-wide transcriptional activity of ASCL1 is unknown. Using human neuroblastoma cells that maintain a rapidly dividing neuroblastic phenotype yet retain the ability to undergo differentiation as a model system, we find that phosphorylation of ASCL1 has limited effect on target gene promoter association, but predominantly regulates its binding to a subset of distal enhancer regions, resulting in extensive differences in target control by activation, as well as direct and indirect gene repression. These genome-wide analyses reveal how post-translational modification of ASCL1 can change its structure and function, driving it to differential regulatory elements to change cell fate, and controlling ASCL1’s activity as a master transcription regulator of neurogenesis. Using functional mutational and pharmacological approaches, we find that preventing CDK-dependent phosphorylation of ASCL1 in neuroblastoma cells results in co-ordinated suppression of the MYC-driven core circuit supporting neuroblast identity and proliferation, while simultaneously activating a gene programme driving neuronal differentiation. Thus, we show targeting the post-translational modification of a key developmental regulator can re-engage a latent genome-wide programme forcing mitotic exit and differentiation in cancer cells.
2021-03-15 | GSE153823 | GEO
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
2016-07-21 | GSE69394 | GEO