Microbes modulate sympathetic neurons via a gut-brain circuit
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ABSTRACT:
PROVIDER: PRJNA608916 | ENA |
REPOSITORIES: ENA
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Project description:Gut-brain connections monitor the intestinal tissue and its microbial and dietary content1, regulating both intestinal physiological functions such as nutrient absorption and motility2,3, and brain–wired feeding behaviour2. It is therefore plausible that circuits exist to detect gut microbes and relay this information to central nervous system (CNS) areas that, in turn, regulate gut physiology4. We characterized the influence of the microbiota on enteric–associated neurons (EAN) by combining gnotobiotic mouse models with transcriptomics, circuit–tracing methods, and functional manipulation. We found that the gut microbiome modulates gut–extrinsic sympathetic neurons; while microbiota depletion led to increased cFos expression, colonization of germ-free mice with short-chain fatty acid–producing bacteria suppressed cFos expression in the gut sympathetic ganglia. Chemogenetic manipulations, translational profiling, and anterograde tracing identified a subset of distal intestine-projecting vagal neurons positioned to play an afferent role in microbiota–mediated modulation of gut sympathetic neurons. Retrograde polysynaptic neuronal tracing from the intestinal wall identified brainstem sensory nuclei activated during microbial depletion, as well as efferent sympathetic premotor glutamatergic neurons that regulate gastrointestinal transit. These results reveal microbiota–dependent control of gut extrinsic sympathetic activation through a gut-brain circuit.
2020-03-20 | GSE145986 | 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
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| S-EPMC7367767 | biostudies-literature
Project description:The objective of this study was to identify genes that are differentially regulated in cultured sympathetic neurons during BMP-induced dendritic growth and to determine the temporal expression patterns of these genes. We determined that inhibiting transcription within the first 24 hours after adding exogenous BMP-7 blocks BMP-induced dendritic growth in cultured sympathetic neurons dissociated from the superior cervical ganglia of embryonic rat pups. Thus, we determined the transcriptional profiles of cultured sympathetic neurons at 6 and 24 hours after addition of BMP-7 to identify early and later transcriptional responses that may drive dendrite formation. We isolated total RNA from sympathetic neurons exposed to three different experimental conditions: (1) no BMP-7 treatment; (2) treatment with BMP-7 for 6 hours; and (3) treatment with BMP-7 for 24 hours. Total RNA was labeled and hybridized to Affymetrix Rat Genome U34A oligonucleotide microarrays. This experiment was independently repeated three times using cultures derived from three independent dissections, such that a total of nine arrays were used. The nine samples were processed over two batches and the batching was balanced across the treatment conditions. Image data was processed using Affymetrix GCOS software to generate numeric, probe level data (CEL) and CEL data was then pre-processed using the RMA algorithm implemented by Partek Genomics Suite (St. Louis, MO). Following batch correction of the probe set level, normalized data using Partek, differential gene expression was determined by two-way ANOVA and linear contrasts between all treatment conditions were applied to generate fold-change values along with the statistical p-value. Lists of significantly changed transcripts were uploaded to MetaCore (GeneGo, ) for mining biological annotation and network analysis.
2011-06-30 | E-GEOD-28150 | 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:IL-13 promotes sensory-sympathetic neurons crosstalk in asthma
2023-03-23 | GSE227968 | GEO
Project description:To investigate and compare the gene expression profile of sympathetic neurons differentiated from healthy hESCs and iPSCs from patient with Familial dysautonomia
2022-10-26 | GSE212255 | GEO
Project description:he neural crest is an embryonic stem cell population unique to vertebrates whose expansion and diversification are thought to have promoted vertebrate evolution by enabling emergence of novel cell types and structures like jaws and peripheral ganglia2. While basal vertebrates have sensory ganglia, convention has it that trunk sympathetic chain ganglia arose only in jawed vertebrates. In contrast, here we report the presence of trunk sympathetic neurons in the sea lamprey, Petromyzon marinus, an extant jawless vertebrate. These neurons arise from sympathoblasts near the dorsal aorta that undergo noradrenergic specification via a transcriptional program homologous to that described in gnathostomes. Lamprey sympathoblasts populate the extracardiac space and extend along the length of the trunk in bilateral streams, expressing the catecholamine biosynthetic pathway enzymes tyrosine hydroxylase and dopamine -hydroxylase. CM-DiI lineage tracing analysis further confirmed that these cells derive from the trunk neural crest. RNA-seq of isolated ammocete trunk sympathoblasts revealed gene profiles characteristic of sympathetic neuron function. Our findings challenge prevailing dogma which posits that sympathetic ganglia are a gnathostome innovation, instead suggesting that a late-developing rudimentary sympathetic nervous system may have been characteristic of the earliest vertebrates.
2024-02-22 | GSE246248 | GEO
Project description:Developing sympathetic neurons depend on nerve growth factor (NGF) for survival and die by apoptosis after NGF withdrawal. This process requires de novo gene expression but only a small number of genes induced by NGF deprivation have been identified so far. We have used Affymetrix Exon arrays to study the pattern of expression of all known genes in sympathetic neurons deprived of NGF. We identified 415 up- and 813 down-regulated genes, including most of the genes previously known to be regulated in this system. By including a mixed lineage kinase (MLK) inhibitor, CEP-11004, in our experimental design we identified which of the genes induced after NGF withdrawal are potential targets of the MLK-JNK-c-Jun pathway. A detailed Gene Ontology and functional enrichment analysis also identified genetic pathways, such as the ER unfolded protein response, that are highly enriched and overrepresented amongst the genes expressed after NGF withdrawal whilst hierarchical cluster analysis revealed four major patterns of gene expression. Five genes not previously studied in sympathetic neurons - trb3, ddit3, txnip, ndrg1 and mxi1 - were validated by real time-PCR. The proteins encoded by these genes also increased in level after NGF withdrawal and this increase was prevented by CEP-11004, suggesting that these genes are potential targets of the MLK-JNK-c-Jun pathway. Overall, our microarray data gives a comprehensive overview of, and provides new information about, signalling pathways and transcription factors that are regulated by NGF withdrawal and identifies potential targets of the MLK-JNK-c-Jun pathway in sympathetic neurons
2013-01-17 | E-MTAB-696 | biostudies-arrayexpress
Project description:The objective of this study was to identify genes that are differentially regulated in cultured sympathetic neurons during BMP-induced dendritic growth and to determine the temporal expression patterns of these genes.
2011-06-30 | GSE28150 | GEO