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: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: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
Project description:Proteomic Data of Orthotopic Renal RENCA Cell Xenografts in Balb/c Mice After Sympathetic Nerve Ablation with 6-OHDA and of the Control Group
2025-10-15 | PXD069465 |
Project description:Hematological malignancies and cytotoxic therapy induce sympathetic neuropathy in the bone marrow (BM), leading to niche remodeling, disease progression, and impaired hematopoiesis regeneration after myeloablative therapy. Vincristine induces pro-inflammatory cytokine production in the BM, including tumor necrosis factor a (TNF-a), impairs hematopoietic stem cell function, and harms sympathetic neurons. Deleting TNF receptor R1 (TNFR1) in sympathetic nerves exacerbated hematopoietic stem cell exhaustion. Mechanistically, loss of sympathetic nerve-specific TNFR1 signaling prevented the increase of norepinephrine levels in the BM after vincristine treatment, leading to delayed inflammation resolution due to elevated IL-6 production by BM endothelial cells. Therefore, TNFR1 signaling in sympathetic nerves plays a role in the resolution of the inflammatory state after vincristine treatment. Therapeutic strategies meant to reduce inflammation should be considered to prevent long-term hematopoietic damage in cancer patients.
2025-08-31 | GSE305591 | GEO