Neuronal-Activity Dependent Mechanisms of Small Cell Lung Cancer Pathogenesis
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PROVIDER: PRJNA1294240 | ENA |
REPOSITORIES: ENA
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Project description:Neuronal-Activity Dependent Mechanisms of Small Cell Lung Cancer Pathogenesis
| PRJNA1091691 | ENA
Project description:Neural activity is increasingly recognized as a crucial regulator of cancer growth. In the brain, neuronal activity robustly influences glioma growth both through paracrine mechanisms and through electrochemical integration of malignant cells into neural circuitry via neuron-to-glioma synapses. Outside of the CNS, innervation of tumors such as prostate, breast, pancreatic and gastrointestinal cancers by peripheral nerves similarly regulates cancer progression. However, the extent to which the nervous system regulates lung cancer progression, either in the lung or when metastatic to brain, is less well understood. Small cell lung cancer (SCLC) is a lethal high-grade neuroendocrine tumor that exhibits a strong propensity to metastasize to the brain. Here we demonstrate that SCLC cells in the brain co-opt neuronal activity-regulated mechanisms to stimulate growth and progression. Glutamatergic and GABAergic cortical neuronal activity each drive proliferation of SCLC in the brain through both paracrine and synaptic neuron-cancer interactions. In the brain, SCLC cells form bona fide neuron-to-SCLC synapses and exhibit depolarizing currents with consequent calcium transients in response to neuronal activity. SCLC cell membrane depolarization is sufficient to promote the growth of intracranial tumors. In the lung, vagus nerve transection markedly inhibits primary lung tumor formation and development, highlighting a critical role for innervation in overall SCLC growth. Taken together, these studies illustrate that neuronal activity plays a crucial role in dictating SCLC pathogenesis in both the lung and the brain.
2025-07-29 | GSE262422 | GEO
Project description:Neural activity is increasingly recognized as a crucial regulator of cancer growth. In the brain, neuronal activity robustly influences glioma growth both through paracrine mechanisms and through electrochemical integration of malignant cells into neural circuitry via neuron-to-glioma synapses. Outside of the CNS, innervation of tumors such as prostate, breast, pancreatic and gastrointestinal cancers by peripheral nerves similarly regulates cancer progression. However, the extent to which the nervous system regulates small cell lung cancer progression, either in the lung or when growing within the brain, is less well understood. Small cell lung cancer (SCLC) is a lethal high-grade neuroendocrine tumor that exhibits a strong propensity to metastasize to the brain. Here we demonstrate that SCLC cells in the brain co-opt neuronal activity-regulated mechanisms to stimulate growth and progression. In the lung, vagus nerve transection markedly inhibits primary lung tumor formation and development, highlighting a critical role for innervation in SCLC growth. In the brain, glutamatergic and GABAergic cortical neuronal activity each drive proliferation of SCLC in the brain through both paracrine and synaptic neuron-cancer interactions. SCLC cells form bona fide neuron-to-SCLC synapses and exhibit depolarizing currents with consequent calcium transients in response to neuronal activity. SCLC cell membrane depolarization is sufficient to promote the growth of intracranial tumors. Taken together, these studies illustrate that neuronal activity plays a crucial role in dictating SCLC pathogenesis in both the lung and the brain.
2025-09-10 | GSE303152 | GEO
Project description:Neuronal Activity-Dependent Gene Dysregulation inC9orf72i3Neuronal Models of ALS/FTD Pathogenesis
| PRJNA1152951 | ENA
Project description:The GGGGCC nucleotide repeat expansion (NRE) mutation in the C9orf72 (C9) gene is the most common cause of ALS and FTD. Neuronal activity plays an essential role in shaping biological processes within both healthy and neurodegenerative disease scenarios. Here, we show that at baseline conditions, C9-NRE iPSC-cortical neurons display aberrations in several pathways, including synaptic signaling and transcriptional machinery, potentially priming diseased neurons for an altered response to neuronal stimulation. Indeed, exposure to two pathophysiologically relevant stimulation modes, prolonged membrane depolarization, or a blockade of K+ channels, followed by RNA sequencing, induces a temporally divergent activity-dependent transcriptome of C9-NRE cortical neurons compared to healthy controls. These findings reveal the impact of neuronal activity on the ALS/FTD-associated transcriptome and may reveal pathways necessary for conferring neuronal resilience or degeneration.
2024-12-31 | GSE275765 | GEO
Project description:BRG1 role in neuronal activity
| PRJNA730575 | ENA
Project description:Neuronal activity induces gene expression programs associated with plasticity in the brain, but it also transiently suppresses gene expression through poorly understood mechanisms. Here, we report that neuronal activity downregulates NEUROD-dependent gene expression in cerebellar granule neurons in adult mice. Using NEUROD1/2 double conditional knockout mice of both sexes, we show that NEUROD binds and activates its target gene enhancers and establishes a three-dimensional genome architecture that facilitates transcription when neuronal activity is low. Moreover, NEUROD antagonizes activity-dependent gene expression programs, including those regulated by MEF2. However, when granule neurons are activated, NEUROD-dependent transcriptional and genome organizing functions are disrupted. Together, these findings reveal NEUROD as a key regulator of transcriptional programs associated with inactive neurons. Our study provides new insights into how neuronal activity reshapes gene transcription and genome architecture in the brain.
2026-01-09 | GSE310753 | GEO
Project description:Neuronal activity induces gene expression programs associated with plasticity in the brain, but it also transiently suppresses gene expression through poorly understood mechanisms. Here, we report that neuronal activity downregulates NEUROD-dependent gene expression in cerebellar granule neurons in adult mice. Using NEUROD1/2 double conditional knockout mice of both sexes, we show that NEUROD binds and activates its target gene enhancers and establishes a three-dimensional genome architecture that facilitates transcription when neuronal activity is low. Moreover, NEUROD antagonizes activity-dependent gene expression programs, including those regulated by MEF2. However, when granule neurons are activated, NEUROD-dependent transcriptional and genome organizing functions are disrupted. Together, these findings reveal NEUROD as a key regulator of transcriptional programs associated with inactive neurons. Our study provides new insights into how neuronal activity reshapes gene transcription and genome architecture in the brain.
2026-01-09 | GSE310752 | GEO
Project description:Neuronal activity induces gene expression programs associated with plasticity in the brain, but it also transiently suppresses gene expression through poorly understood mechanisms. Here, we report that neuronal activity downregulates NEUROD-dependent gene expression in cerebellar granule neurons in adult mice. Using NEUROD1/2 double conditional knockout mice of both sexes, we show that NEUROD binds and activates its target gene enhancers and establishes a three-dimensional genome architecture that facilitates transcription when neuronal activity is low. Moreover, NEUROD antagonizes activity-dependent gene expression programs, including those regulated by MEF2. However, when granule neurons are activated, NEUROD-dependent transcriptional and genome organizing functions are disrupted. Together, these findings reveal NEUROD as a key regulator of transcriptional programs associated with inactive neurons. Our study provides new insights into how neuronal activity reshapes gene transcription and genome architecture in the brain.
2026-01-09 | GSE310749 | GEO
Project description:BRG1 regulates neuronal activity-dependent gene activation [RNA-seq_A]
| PRJNA730576 | ENA