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SRP174375
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2500
Description
Sensory functions of the vagus nerve are critical for specific aware perceptions and for monitoring visceral functions in the cardio-pulmonary and gastrointestinal systems. Here we present a comprehensive identification, classification, and validation of the neuron types in the neural crest (jugular) and placode (nodose) derived vagal ganglia by single cell transcriptomic (scRNA-seq) analysis. Our results reveal major differences between neurons derived from different embryonic origins. Jugular neurons exhibit fundamental similarities to the somatosensory spinal neurons, including major types such as C-low threshold mechanoreceptors (C-LTMRs), A-LTMRs, Ad-nociceptors, cold-, and mechano-heat C-nociceptors. In contrast, the nodose ganglion contains 18 distinct types dedicated to surveying the physiological state of the internal body. Our results reveal a vast diversity of vagal neuron types including many previously unanticipated types as well as proposed types that are consistent with chemoreceptors, nutrient detectors, baroreceptors, and stretch and volume mechanoreceptors of the respiratory, gastrointestinal, and cardiovascular systems. Overall design: Single-cell RNA-seq from 1896 vagal ganglion cells derived from wild-type and Vglut2Cre-Tomato animals originating from four replicates and consisting of the neuronal and non-neuronal cells that make up the ganglionic tissue.
Publication Title
An Atlas of Vagal Sensory Neurons and Their Molecular Specialization.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 44 Downloadable Samples
Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Objective: Physical exercise and vitamin E are considered effective treatments of nonalcoholic fatty liver and other metabolic diseases. However, vitamin E has also been shown to interfere with the adaptation to exercise training, in particular for the skeletal muscle. Here, we studied the hypothesis that vitamin E also interferes with the metabolic adaptation of the liver to acute exercise.
Publication Title
A Vitamin E-Enriched Antioxidant Diet Interferes with the Acute Adaptation of the Liver to Physical Exercise in Mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Muscle contraction during exercise is the major stimulus for the release of peptides and proteins (myokines) that are supposed to take part in the benefical adaptation to exercise. We hypothesize that application of an in vitro exercise stimulus as electric pulse stimulation (EPS) to human myotubes enables the investigation of the human muscle secretome in a clearly defined model. We applied EPS for 24 h to primary human myotubes and studied the whole genome-wide transcriptional response and as well as the release of candidate myokines. We observed 183 differentially regulated transcripts with fold-changes > 1.3. The transcriptional response resembles several properties of the in vivo situation in the skeletal muscle after endurance exercise, namely significant enrichment of pathways associated with interleukin and chemokine signaling, lipid metabolism, and anti-oxidant defense; notably without increased release of creatin kinase.
Publication Title
Cytokine response of primary human myotubes in an in vitro exercise model.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 302 Downloadable Samples
- Illumina HiSeq 2000
Description
We explore the heterogeneity of mouse thoracic ganglia demonstrating the presence of an unexpected variety of cell-types and identify specialized populations of nipple- and pilo-erector muscle neurons. These neurons extend axonal projections and are born amongst other neurons during embryogenesis, but remain unspecialized until target organogenesis occurs postnatally. Target innervation and cell-type specification is coordinated by an intricate acquisition of unique combinations of growth factor receptors and the initiation of expression of concomitant ligands by the nascent erector muscles. Overall design: RNA-seq analysis of 298 single sympathetic neuronal cells from the mouse thoracic ganglion
Publication Title
Visceral motor neuron diversity delineates a cellular basis for nipple- and pilo-erection muscle control.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Background/aims: Serum concentrations of the hepatokine fibroblast growth factor (FGF) 21 are elevated in obesity, type2 diabetes, and the metabolic syndrome. We asked whether FGF21 levels differ between subjects with metabolically healthy vs. unhealthy obesity (MHO vs. MUHO) opening the possibility that FGF21 is a crosstalker between liver and adipose tissue in MUHO. Furthermore, we studied the effects of chronic FGF21 treatment on adipocyte differentiation, lipid storage, and adipokine secretion.
Publication Title
Fibroblast growth factor 21 is elevated in metabolically unhealthy obesity and affects lipid deposition, adipogenesis, and adipokine secretion of human abdominal subcutaneous adipocytes.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We performed gene expression microarray analysis of skeletal muscle biopsies from normal glucose tolerant subjects and type 2 diabetes subjects obtained during a 60 min bicycle ergometer exercise and the 180 min of recovery phase
Publication Title
Type 2 diabetes alters metabolic and transcriptional signatures of glucose and amino acid metabolism during exercise and recovery.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 56 Downloadable Samples
- Illumina HiSeq 4000
Description
Missense mutations in coding region of PDX1 predispose to type-2 diabetes mellitus as well as cause MODY through largely unexplored mechanisms. Here, we screened a large cohort of subjects with increased risk for diabetes and identified two subjects with impaired glucose tolerance carrying heterozygous missense mutations in the PDX1 coding region leading to single amino acid exchanges (P33T, C18R) in its transactivation domain. We generated iPSCs from patients with heterozygous PDX1P33T/+, PDX1C18R/+ mutations and engineered isogenic cell lines carrying homozygous PDX1P33T/P33T, PDX1C18R/C18R mutations and a heterozygous PDX1 loss-of-function mutation (PDX1+/-). Using an in vitro ß-cell differentiation protocol, we demonstrated that both PDX1P33T/+, PDX1C18R/+ and PDX1P33T/P33T, PDX1C18R/C18R mutations impair ß-cell differentiation and function. Furthermore, PDX1+/- and PDX1P33T/P33T mutations reduced differentiation efficiency of pancreatic progenitors (PPs), due to downregulation of PDX1-bound genes, including transcription factors MNX1 and PDX1 as well as insulin resistance gene CES1. Additionally, both PDX1P33T/+ and PDX1P33T/P33T mutations in PPs reduced the expression of PDX1-bound genes including the long-noncoding RNA, MEG3 and the imprinted gene NEURONATIN, both involved in insulin synthesis and secretion. Our results reveal mechanistic details of how diabetes-associated PDX1 point mutations impair human pancreatic endocrine lineage formation and ß-cell function and contribute to pre-disposition for diabetes. Overall design: We performed RNA-seq of control and isogenic PDX1 mutant cell lines at PP stage
Publication Title
Point mutations in the PDX1 transactivation domain impair human β-cell development and function.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
substantial number of people at risk to develop type 2 diabetes could not improve insulin sensitivity by physical training intervention. We studied the mechanisms of this impaired exercise response in 20 middle-aged individuals who performed a controlled eight weeks cycling and walking training at 80 % individual VO2max. Participants identified as non-responders in insulin sensitivity (based on Matsuda index) did not differ in pre-intervention parameters compared to high responders. The failure to increase insulin sensitivity after training correlates with impaired up-regulation of mitochondrial fuel oxidation genes in skeletal muscle, and with the suppression of the upstream regulators PGC1 and AMPK2. The muscle transcriptome of the non-responders is further characterized by an activation of TGF and TGF target genes, which is associated with increases in inflammatory and macrophage markers. TGF1 as inhibitor of mitochondrial regulators and insulin signaling is validated in human skeletal muscle cells. Activated TGF1 signaling down-regulates the abundance of PGC1, AMPK2, mitochondrial transcription factor TFAM, and of mitochondrial enzymes. Thus, increased TGF activity in skeletal muscle can attenuate the improvement of mitochondrial fuel oxidation after training and contribute to the failure to increase insulin sensitivity.
Publication Title
TGF-β Contributes to Impaired Exercise Response by Suppression of Mitochondrial Key Regulators in Skeletal Muscle.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The Skeletal muscle is a metabolic active tissue that secretes various proteins. These so called myokines act auto-, para- and endocrine affecting muscle physiology and exert systemic effects on other tissues and organs. Myokines are also described to play a crucial role in the pathophysiology of metabolic diseases.
Publication Title
Secretome profiling of primary human skeletal muscle cells.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide analysis of PDX1 target genes in human pancreatic progenitors.
Sample Metadata Fields
Specimen part
View Samples