Retrograde signaling from axon to soma activates intrinsic regeneration mechanisms in lesioned peripheral sensory neurons; however, the links between axonal injury signaling and the cell body response are not well understood. Here, we used phosphoproteomics and microarrays to implicate ~900 phosphoproteins in retrograde injury signaling in rat sciatic nerve axons in vivo and ~4500 transcripts in the in vivo response to injury in the dorsal root ganglia. Computational analyses of these data sets identified ~400 redundant axonal signaling networks connected to 39 transcription factors implicated in the sensory neuron response to axonal injury. Experimental perturbation of individual overrepresented signaling hub proteins, including Abl, AKT, p38, and protein kinase C, affected neurite outgrowth in sensory neurons. Paradoxically, however, combined perturbation of Abl together with other hub proteins had a reduced effect relative to perturbation of individual proteins. Our data indicate that nerve injury responses are controlled by multiple regulatory components, and suggest that network redundancies provide robustness to the injury response
Signaling to transcription networks in the neuronal retrograde injury response.
No sample metadata fields
View SamplesGene expression analysis of motor cortex after spinal C3 lesion
A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program.
Sex, Specimen part, Time
View SamplesWe demonstrate for the first time that the extracellular matrix glycoprotein Tenascin-C regulates the expression of key patterning genes during late embryonic spinal cord development, leading to a timely maturation of gliogenic neural precursor cells. We first show that Tenascin-C is expressed by gliogenic neural precursor cells during late embryonic development. The loss of Tenascin-C leads to a sustained generation and delayed migration of Fibroblast growth factor receptor 3 expressing immature astrocytes in vivo. Furthermore, we could demonstrate an upregulation of Nk2 transcription factor related locus 2 (Nkx2.2) and its downstream target Sulfatase 1 in vivo. A dorsal expansion of Nkx2.2-positive cells within the ventral spinal cord indicates a potential progenitor cell domain shift. Moreover, Sulfatase 1 is known to regulate growth factor signalling by cleaving sulphate residues from heparan sulphate proteoglycans. Consistent with this possibility we observed changes in both Fibroblast growth factor 2 and Epidermal growth factor responsiveness of spinal cord neural precursor cells. Taken together our data clearly show that Tenascin-C promotes the astroglial lineage progression during spinal cord development.
The extracellular matrix molecule tenascin C modulates expression levels and territories of key patterning genes during spinal cord astrocyte specification.
Specimen part
View SamplesStudies in rodents and newborn humans, demonstrate the influence of brown adipose tissue (BAT) in temperature control and energy balance, which also has a critical role in the regulation of body weight. Here, we obtained samples of epicardial adipose tissue (EAT) from neonates, infants and children in order to compare the changes in gene expression with age
Gene pathway development in human epicardial adipose tissue during early life.
Sex, Specimen part
View Samplescharacterize the molecular signature of PB-IMC in different stages of tumor development, thus possibly leading to a novel, sensitive and elegant approach for early cancer detection and surveillance. Overall design: Two types of cancer. For each type 4 groups (day 0, day 4, day 8, day 11), for each group 3 biological repeats
The transcriptional profile of circulating myeloid derived suppressor cells correlates with tumor development and progression in mouse.
Specimen part, Cell line, Subject
View SamplesWe studied the KRAS and NRAS mutational status in pediatric MLL-AF4+ leukemia patients by means of ultra deep amplicon sequencing. The gene expression profiles of RAS wild type and RAS mutated patients were investigated by gene expression analysis. We showed that mutated patients were characterized by a RAS related expression signature.
Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis.
Specimen part, Disease, Disease stage, Subject
View SamplesAutoimmune pancreatitis (AIP) is a recently identified disease of the pancreas with unknown etiology and antigens. The aim of this study was to determine new target antigens and differentially regulated genes and proteins by means of transcriptomics and proteomics and to validate them in patients with autoimmune pancreatitis. Here we report a distinct downregulation at the RNA and protein level of pancreatic proteases (anionic trypsinogen, cationic trypsinogen, mesotrypsinogen, elastase IIIB) and pancreatic stone protein in autoimmune pancreatitis in comparison to alcohol-induced chronic pancreatitis.
Autoantibodies against the exocrine pancreas in autoimmune pancreatitis: gene and protein expression profiling and immunoassays identify pancreatic enzymes as a major target of the inflammatory process.
Sex, Age, Specimen part, Disease
View SamplesBackground: Moderate hypothermia (32oC for 12 72 hours) has therapeutic applications, but the mechanisms by which it affects cellular function are unclear. We tested the hypothesis that moderate hypothermia produces broad changes in gene expression by human cells at the level of mRNA.
Effect of moderate hypothermia on gene expression by THP-1 cells: a DNA microarray study.
No sample metadata fields
View SamplesLong-term maintenance of spermatogenesis in mammals is supported by GDNF, an essential growth factor required for spermatogonial stem cell (SSC) self-renewal. Exploiting a transgenic GDNF overexpression model, which expands and normalizes the pool of undifferentiated spermatogonia between Plzf +/+ and Plzf lu/lu mice, we used RNAseq to identify a rare subpopulation of cells that express EOMES, a T-box transcription factor. Lineage tracing, conditional ablation, and busulfan challenge show that these are long-term SSCs that contribute to steady state spermatogenesis as well as regeneration following chemical injury. EOMES+ SSCs have a lower proliferation index than EOMES- GFRA1+ spermatogonia in wild-type but not in Plzf lu/lu mice. This comparison demonstrates that PLZF regulates their proliferative activity and suggests that EOMES+ SSCs are lost through proliferative exhaustion in Plzf lu/lu mice. Single cell RNA sequencing of EOMES+ cells from Plzf +/+ and Plzf lu/lu mice support a hierarchical model of a slow-cycling long-term SSC population supporting more rapid-cycling short-term SSCs. Overall design: 384-well plate-based 3'-end scRNA-seq was performed on two groups, Plzf +/+ and Plzf lu/lu, of cells across 4 plates. Plzf +/+ cells were spread across 2 plates and Plzf lu/lu cells were spread over 1 plate. The 4th plate contains both Plzf lu/lu (up to well C15) and Plzf +/+ (well C15 onward). Each sample in this record represents one plate.
Identification of EOMES-expressing spermatogonial stem cells and their regulation by PLZF.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Response of gastric epithelial progenitors to Helicobacter pylori Isolates obtained from Swedish patients with chronic atrophic gastritis.
Age, Specimen part, Treatment
View Samples