Genome-wide studies of sympathetic neuron development
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA360582 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5163060.fastq.gz | Fastqsanger.gz | |||
| SRR5163070.fastq.gz | Fastqsanger.gz | |||
| SRR5163071.fastq.gz | Fastqsanger.gz | |||
| SRR5163072.fastq.gz | Fastqsanger.gz | |||
| SRR5163065.fastq.gz | Fastqsanger.gz |
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Project description:Understanding factors that drive development and function of the sympathetic neuron is crucial to development of potential therapies for neuroblastoma. Here, we identify a key cell autonomous role for the LIM homeodomain transcription factor ISL1 for survival, proliferation and differentiation of sympathetic neurons throughout development. Analysis of several Isl1 mutant mouse lines, including one in which Isl1 was specifically ablated in sympathetic neuron (Wnt1-cre;Isl1 f/f) revealed an early requirement for Isl1 within sympathetic neurons for proliferation and surrvial. RNA-seq analyses on sympathetic neurons revealed dysregulation of a number of genes critical for sympathetic neuron development .Our studies demonstrated that ISL1 regulated the peoliferation, surrvial and differentiation.
2017-11-09 | GSE93306 | GEO
Project description:Understanding factors that drive development of the sympathetic neuron is crucial to development of potential therapies for neuroblastoma. Here, we identify a key cell autonomous role for the LIM homeodomain transcription factor ISL1 for survival, proliferation and differentiation of sympathetic neurons throughout development. Chromatin immunoprecipitation assays performed utilizing antibody to ISL1 in chromatin extracts from sympathetic neurons demonstrated that ISL1 directly binds genomic regions within several genes critical for sympathetic neuron development and function, including subunits of the Insm1, Lmo1,Tlx3 and Prox1. Our studies represent in vivo ChIP-seq studies for sympathetic neurons which provide a basis for further exploration of factors critical to sympathetic neurons development and function .
2017-11-09 | GSE93304 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-11-09 | GSE93308 | 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:Adrenal chromaffin cells and sympathetic neuron are derived from neural crest precursors and both cell types can give rise to childhood cancer, neuroblastoma. However only limited is known about the mechanism of their development. Better understanding of their transcriptomic profiles during development could gives an insight into the cell fates acquisition as well as the origin of neuroblastoma. Yellow fluorescent protein expressing sympathetic neuroblasts and adrenal chromaffin cells were isolated from E12.5 TH-IRES-Cre;ROSA26-EYFP mouse embryos by fluorescence-activated cell sorting. Transcriptomic profiles of sympathetic neuroblasts and adrenal chromaffin cells from embryonic age (E)12.5 TH-IRES-Cre;ROSA26-EYFP mice were generated by RNA sequencing, in four paired biological replicates.
2019-05-24 | E-MTAB-7086 | biostudies-arrayexpress
Project description:Neurons derived from human pluripotent stem cells (hPSCs) are a remarkable tool for modeling human neural development and diseases. However, it remains largely unknown whether the hPSC-derived neurons can be functionally coupled with their target tissues in vitro, which is essential for understanding inter-cellular physiology and further translational studies. Here, we demonstrate that hPSC-derived sympathetic neurons can be obtained from hPSCs and that the resulting neurons form physical and functional connections with cardiac muscle cells. By use of multiple hPSC reporter lines, we recapitulated human autonomic neuron development in vitro, and successfully isolated PHOX2B::eGFP+ neurons exhibiting sympathetic marker expression, electrophysiological properties, and norepinephrine secretion. With pharmacological and optogenetic manipulations, the PHOX2B::eGFP+ neurons controlled the beating rates of cardiomyocytes, and their physical interaction led to neuronal maturation. Our study lays a foundation for the specification of human sympathetic neurons and for the hPSC-based neuronal control of end organs in a dish. Using the four genetic reporter systems (OCT4::eGFP, SOX10::eGFP, ASCL1::eGFP, and PHOX2B::eGFP reporter hESC lines), we were able to purify discrete cell populations at four differentiation stages, recapitulating the sympathoadrenal differentiation process in vitro with purified and defined populations in four specific differentiation stages. We performed transcriptome analysis of OCT4::eGFP+ cells (3 biological replicates, representing undifferentiated hESCs), SOX10::eGFP+ cells (3 biological replicates, multi-potent neural crest), ASCL1::eGFP+ cells (3 biological replicates, putative sympathoadrenal progenitors), and PHOX2B::eGFP+ cells (2 biological replicates, putative sympathetic neuronal precursors).
2016-07-01 | E-GEOD-80689 | biostudies-arrayexpress
Project description:Sympathetic Neuron Hyperactivation Drives Hair Follicle Necrosis and T Cell Autoreactivity
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Project description:We performed single-cell RNA-seq (10x Chromium 3' v.3.1) on dissociated single cell suspensions from mouse (C57BL/6) celiac and superior mesenteric sympathetic ganglia to determine transcriptomic cell types. We identified sympathetic neuron types that specifically innervate unique combinations of visceral organs and control physiological functions.
2024-10-02 | GSE278457 | GEO
Project description:The cellular mechanism(s) linking macrophages to norepinephrine (NE)-mediated regulation of thermogenesis has been a topic of debate. Here, we identify sympathetic neuron-associated macrophages (SAMs) as a population of macrophages that mediate clearance of NE via expression of Slc6a2, an NE transporter, and monoamine oxidase A (MAOa), a degradation enzyme. Optogenetic activation of the SNS upregulates NE uptake by SAMs and shifts the SAM profile to a more pro-inflammatory state. NE uptake by SAMs is prevented by genetic depletion of Slc6a2 or inhibition of the transporter. We also found that obesity increases SAM content in the SNS. In two mouse models of obesity, genetic ablation of Slc6a2 in SAMs increases brown adipose tissue (BAT) content, causes browning of white fat, increases thermogenesis and leads to significant and sustained weight loss. We further show that this pathway is conserved as human sympathetic ganglia also contain SAMs and the analogous molecular machinery for NE clearance, thus constituting a potential target for obesity treatment.
2017-10-09 | GSE103847 | GEO
Project description:The sympathetic ganglia are essential components of the nervous system that regulate various aspects of involuntary body functions. Recapitulating sympathetic ganglion development with three-dimensional (3D) organoids is challenging and has not been achieved. Here, we report a method to differentiate human pluripotent stem cells into 3D neural organoids that resemble peripheral sympathetic ganglia, producing both neurons and glial cells of the ganglia in a self-organized manner. We developed an organoid system to construct functional connections between the sympathetic ganglia and one of their peripheral targets, the heart, by fusing human sympathetic ganglion organoids (hSGOs) and heart-forming organoids. Notably, this system enables the evaluation of signaling controls (i.e., nerve growth factor [NGF] signaling) on human sympathetic-to-cardiac innervation and reveals the reciprocal impacts between the sympathetic and cardiac lineages during their co-development. Our study provides a physiologically relevant platform for understanding the development of human sympathetic ganglia, their crosstalk with peripheral targets, and related diseases.
2025-12-11 | GSE294956 | GEO