Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1129022 | ENA |
REPOSITORIES: ENA
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Project description:Adult stem cell activity and organ development are elaborately regulated by microenvironmental signals. However, little is known about the regulatory effects of microenvironmental sympathetic nerve signals on organ development and stem cell activity. Here, using a mouse mammary gland model, we determined the regulatory function of sympathetic nerve system (SNS) on mammary development and mammary stem cell activity. Our results indicated that depletion of sympathetic nerve signals delayed the elongation of mammary ducts during puberty and pregnancy, and lead to the loss of mammary stem cells (MaSCs). In vitro three-dimensional (3D) culture and in vivo transplantation analyses indicated that the loss of sympathetic nerve signals inhibits the self-renewal and reconstruction activity of mammary stem cells, while the activation of sympathetic nerve signals promotes the self-renewal and reconstruction activity of mammary stem cells. Mechanistically, we found that sympathetic nerve signals regulate the activity of mammary stem cells and mammary development through the PI3K/ERK pathway. Together, our study reveals the function of sympathetic nervous signals in maintaining mammary homeostasis and regulating mammary stem cell activity, providing a novel view for the nervous system's regulation of organ development.
2024-11-06 | GSE243652 | GEO
Project description:Pancreatic cancer is a highly innervated gastrointestinal disease in which sympathetic nerves play a critical role in modulating tumor growth and the tumor microenvironment (TME). While recent studies suggest that sympathetic nerves influence various TME components, including lymphoid and myeloid immune cells, their interactions with cancer-associated fibroblasts (CAFs) remain poorly understood. CAFs are a hallmark of pancreatic tumors and are known to upregulate axon guidance and neuroactive cues, suggesting a potential feedback loop with tumor-innervating nerves. Here, we investigated the bidirectional crosstalk between sympathetic nerves and CAFs in human and mouse pancreatic tumors. Using a chemo-genetic ablation model, we selectively eliminated pancreatic sympathetic nerves and found that denervation significantly reduced tumor size in female mice. To further dissect this interaction, we established co-culture systems with immortalized pancreatic fibroblasts and primary sympathetic neuron explants, identifying key transcriptional changes driven by CAF-sympathetic nerve signaling. Our findings demonstrate that sympathetic signaling enhances CAF activation and extracellular matrix remodeling, while activated CAFs, in turn, induce transcriptional programs in sympathetic neurons associated with nerve injury response. These results establish CAFs as central mediators of the tumor-supportive role of sympathetic nerves, offering new insights into the neural regulation of pancreatic cancer progression.
2026-02-12 | GSE318481 | GEO
Project description:The melanocortin system is a brain circuit that influences energy balance by regulating energy intake and expenditure. In addition, the brain-melanocortin system controls adipose tissue metabolism to optimize fuel mobilization and storage. Specifically, increased brain-melanocortin signaling or negative energy balance promotes lipid mobilization by increasing Sympathetic Nervous input to adipose tissue. In contrast, calorie-independent mechanisms favoring energy storage are less understood. Here we demonstrate that obesogenic signals, including reduction of brain-melanocortin signaling or high-fat feeding, actively promote fat mass gain independently of caloric intake via efferent nerve fibers conveyed by the common hepatic branch of the vagus nerve. These signals promote adipose tissue expansion by activating lipogenic program and adipocyte and endothelial cell proliferation independently of insulin action or the sympathetic tone to adipose tissue. These data reveal a novel physiological mechanism whereby the brain controls energy stores that may contribute to increased susceptibility to obesity.
2019-04-18 | GSE128383 | GEO
Project description:The sympathetic nervous system controls a wide spectrum of bodily functions including operation of vessels, cardiac rhythm, and the “flight or fight response”. Sympathetic neurons, which are neural crest-derived, develop in coordination with presynaptic motor nerves extending from the central nervous system (CNS). By using nerve-selective genetic ablations, we revealed that sympathetic ganglia development depends on CNS-derived motor innervation. In the absence of preganglionic motor nerves, trunk sympathetic chain ganglia were fragmented and smaller in size, while cervical ganglia were severely misshapen. Sympathetic neurons were misplaced along sensory fibers and projected towards abnormal paths, in some cases invading the sensory dorsal root ganglia. The misplaced progenitors of sympathoblasts corresponded to the nerve-associated, neural crest-derived Schwann cell precursors (SCPs). Notably, we found that SCPs activate the autonomic marker PHOX2B while migrating along motor nerves towards the region of the dorsal aorta in wildtype embryos, suggesting that SCP differentiate into sympathetic neurons while still nerve-associated in motor-ablated embryos. Ligand-receptor prediction from single cell transcriptomic data coupled with functional studies identified Semaphorin 3A/3F as candidate motor nerve-derived signals influencing neural crest migration along axons. Thus, motor nerves control the placement of sympathoblasts and their subsequent axonal navigation during critical periods of sympathetic chain development.
2024-07-14 | GSE261748 | GEO
Project description:Understanding the dynamic changes of cells during calvarial bone repair is crucial for identifying novel therapeutic targets to enhance bone regeneration. However, the cellular changes and intercellular communication during calvarial defect repair remain poorly understood. To address this, we performed single-cell RNA sequencing on tissues collected at different time points post-defect. Our analysis revealed a significant enhancement in intercellular communication following defect, particularly among stem cells, endothelial cells, pericytes, and macrophages. Pathways related to neurogenesis were significantly enriched after defect. Furthermore, we found that inhibiting sympathetic nerves promoted calvarial bone repair. Mechanistically, sympathetic nerve inhibition enhanced angiogenesis and osteogenesis by promoting interactions between pericytes and endothelial cells, generating a novel senescenced Arg1+ macrophages, which contributed to bone repair by secreting osteogenesis-related cytokines. Besides, inhibition of sympathetic nerves promotes the generation of Shisa3+ suture cell subpopulation and enhances osteogenic differentiation capacity. Importantly, senolytics abrogated the repair benefits brought about by sympathetic nerve inhibition, underscoring the critical role of senescent macrophages in the repair process.
2025-12-31 | GSE298251 | GEO
Project description:Pathological role and the mechanism of psychological stress in cancer progression are little known. Here, we show in a mouse model that psychological stress drives pancreatic ductal adenocarcinoma (PDAC) progression via stimulating tumor nerve innervation. We demonstrate that nociception and other stressors activate sympathetic nerve to release Noradrenaline, downregulating tumor cell RNA demethylase alkB homolog 5 (Alkbh5). Alkbh5 deficiency causes cancer cell aberrant m6A modification of RNAs, which are packed to extracellular vesicles and delivered to neurons in the tumor microenvironment, enhancing hyperinnervation and PDAC progression. ALKBH5 levels are reversely correlated with tumor innervation and survival time in PDAC patients. Animal experiments identify a natural flavonoid Fisetin preventing neurons from taking in m6A-RNA contained EVs and suppress PDAC tumor excessive innervation and progression. Together, our study shed light on a novel molecular mechanism for neuro-cancer crosstalk linking psychological stress and cancer progression and raise a potential strategy for PDAC therapy.
2025-03-26 | GSE278755 | GEO
Project description:Pathological role and the mechanism of psychological stress in cancer progression are little known. Here, we show in a mouse model that psychological stress drives pancreatic ductal adenocarcinoma (PDAC) progression via stimulating tumor nerve innervation. We demonstrate that nociception and other stressors activate sympathetic nerve to release Noradrenaline, downregulating tumor cell RNA demethylase alkB homolog 5 (Alkbh5). Alkbh5 deficiency causes cancer cell aberrant m6A modification of RNAs, which are packed to extracellular vesicles and delivered to neurons in the tumor microenvironment, enhancing hyperinnervation and PDAC progression. ALKBH5 levels are reversely correlated with tumor innervation and survival time in PDAC patients. Animal experiments identify a natural flavonoid Fisetin preventing neurons from taking in m6A-RNA contained EVs and suppress PDAC tumor excessive innervation and progression. Together, our study shed light on a novel molecular mechanism for neuro-cancer crosstalk linking psychological stress and cancer progression and raise a potential strategy for PDAC therapy.
2025-03-26 | GSE261936 | GEO
Project description:Snakes possess a unique sensory system for detecting infrared radiation, enabling them to generate a ‘thermal image’ of predators or prey. Infrared signals are initially received by the pit organ, a highly specialized facial structure that is innervated by nerve fibers of the somatosensory system. How this organ detects and transduces infrared signals into nerve impulses is not known. Here we use an unbiased transcriptional profiling approach to identify TRPA1 as the infrared receptor on sensory neurons that innervate the pit organ. TRPA1 from pit bearing snakes (rattlesnakes and pythons) are the most heat sensitive vertebrate ion channels thus far identified, consistent with their role as primary transducers of infrared stimuli in these animals. Thus, snakes detect infrared signals through a mechanism involving radiant heating of the pit organ, rather than photochemical transduction. These findings illustrate the broad evolutionary tuning of TRP channels as thermosensors in the vertebrate nervous system. Gene expression measurements implicate TRPA1 as the heat-sensitive channel in diverse pit snakes
2010-03-16 | E-GEOD-19911 | biostudies-arrayexpress
Project description:This study investigated the role of sympathetic denervation in enhancing CAR T cell anti-tumor efficacy in renal clear cell carcinoma. By blocking the NGF pathway with antibodies, we demonstrated reduced sympathetic nerve distribution and delayed tumor progression. Furthermore, CAR T cells engineered to secrete NGF scFv achieved tumor immunosympathectomy, leading to improved anti-tumor effects. RNA sequencing revealed that this enhancement was linked to reduced terminal exhaustion in CD8 T cells and inhibited macrophage polarization from M1 to M2, promoting a robust anti-tumor immune state. Additionally, splenic T cells exhibited a stronger immune effector phenotype following the infusion of NGF scFv-secreting CAR T cells. These findings suggest that immunosympathectomy may represent a novel strategy to mitigate tumor-induced immunosuppression and improve CAR T cell efficacy in solid tumors.
2024-12-18 | GSE279394 | GEO
Project description:This study investigated the role of sympathetic denervation in enhancing CAR T cell anti-tumor efficacy in renal clear cell carcinoma. By blocking the NGF pathway with antibodies, we demonstrated reduced sympathetic nerve distribution and delayed tumor progression. Furthermore, CAR T cells engineered to secrete NGF scFv achieved tumor immunosympathectomy, leading to improved anti-tumor effects. RNA sequencing revealed that this enhancement was linked to reduced terminal exhaustion in CD8 T cells and inhibited macrophage polarization from M1 to M2, promoting a robust anti-tumor immune state. Additionally, splenic T cells exhibited a stronger immune effector phenotype following the infusion of NGF scFv-secreting CAR T cells. These findings suggest that immunosympathectomy may represent a novel strategy to mitigate tumor-induced immunosuppression and improve CAR T cell efficacy in solid tumors.
2024-12-18 | GSE279393 | GEO