A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. While active hematopoietic stem cell (HSC) contribution to multilineage hematopoiesis is the foundation of clinical HSC transplantation, recent reports have questioned the physiological contribution of HSCs to normal/steady-state adult hematopoiesis. Here, we use inducible lineage tracing from genetically marked adult HSCs and reveal robust HSC-derived multilineage hematopoiesis. This commences via defined progenitor cells, but varies substantially in between different hematopoietic lineages. By contrast, adult HSC contribution to hematopoietic cells with proposed fetal origins is neglible. Finally, we establish that the HSC contribution to multilineage hematopoiesis declines with increasing age. Therefore, while HSCs are active contributors to native adult hematopoiesis, it appears that the numerical increase of HSCs is a physiologically relevant compensatory mechanism to account for their reduced differentiation capacity with age Overall design: Lineage tracing from adult/aged HSCs in steady state
Murine HSCs contribute actively to native hematopoiesis but with reduced differentiation capacity upon aging.
Age, Specimen part, Cell line, Subject
View SamplesPrevious studies have shown that treatment with the somatostatin analogue octreotide LAR causes regression of gastric ECL-cell carcinoids in patients with hypergastrinaemia due to chronic atrophic gastritis, reducing both the number and size of tumours. The main objective of the present study was to examine the molecular mechanisms behind the antiproliferative effect of octreotide in the oxyntic mucosa on a genome wide scale. Female Sprague-Dawley rats were dosed with octreotide LAR and control group were given the LAR vehicle for 21 days. Serum gastrin levels were measured and tissue samples for histology and RNA extraction collected from the oxyntic mucosa. Histomorphological examination showed a significant decrease in the number of gastric glands, cells per gland and length of glands, indicating a negative effect of octreotide on growth of the oxyntic mucosa. Further immunohistochemical studies showed a tendency towards increased apoptosis and decreased proliferation in the group receiving octreotide. Affymetrix GeneChip microarrays were used to detect differentially expressed genes. Many regulated genes could be related to regulation of apoptosis, fewer to proliferation, and the largest group of regulated genes was transcriptional factors several of which may be involved in regulation of growth. Control studies using quantitative real-time RT-PCR showed a high degree of consistency of the microarray results. In conclusion, octreotide exerts a negative effect on growth of the oxyntic mucosa, and extensive gene expression changes relevant to growth regulation can be detected.
Octreotide induces apoptosis in the oxyntic mucosa.
No sample metadata fields
View SamplesGene expression analysis of purified hematopoietic stem and progenitor cells isolated from low to intermediate risk MDS patients and age-matched normal healthy controls. Overall design: Analysis of lineage associated genes and PCA clustering of populations
Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo.
No sample metadata fields
View SamplesInfluenza virus infection-induced gene expression changes of regional B cells are mediated at least in part through type I Interferon:
Influenza virus infection causes global respiratory tract B cell response modulation via innate immune signals.
Sex, Specimen part
View SamplesExperiment 1: U133A arrays (2) hybridized to duplicate sscDNA samples prepared from 20 ng Clontech UHR RNA
Increased DNA microarray hybridization specificity using sscDNA targets.
No sample metadata fields
View SamplesOur study demonstrates that neutrophils infiltrate early-stage PTEN-deficient uterine tumors and oppose tumor growth and malignant progression by inducing detachment and ultimately promoting cell death of tumor cells. This RNA-seq study examined the expression profiles of these uterine epithelial tumor cells in the presence versus absence of neutrophil infiltration. Overall design: Tumor cells from 4-week-old tumor-bearing neutrophil-sufficient versus -deficient mice were isolated by fluorescence activated cell sorting, RNA was isolated, and expression profiles were analyzed by deep sequencing.
Neutrophils Oppose Uterine Epithelial Carcinogenesis via Debridement of Hypoxic Tumor Cells.
Age, Specimen part, Subject
View SamplesThis series represents isolated alveolar macrophages from human subjects.
A distinctive alveolar macrophage activation state induced by cigarette smoking.
No sample metadata fields
View SamplesPatients with systemic lupus erythematosus (SLE) have a markedly increased risk to develop cardiovascular disease, and traditional cardiovascular risk factors fail to account for this increased risk. We used microarray to probe the platelet transcriptome in individuals with SLE and healthy controls, and the gene and protein expression of a subset of differentially expressed genes was further investigated and correlated to platelet activation status. Real-time PCR was used to confirm a type I interferon (IFN) gene signature in patients with SLE, and the IFN-regulated proteins PRKRA, IFITM1 and CD69 (p<0.0001) were found to be up-regulated in platelets from SLE patients as compared to healthy volunteers. Notably, patients with a history of vascular disease had increased expression of type I IFN-regulated proteins as well as more activated platelets as compared with patients without vascular disease. We suggest that interferogenic immune complexes stimulate production of IFN which up-regulates the megakaryocytic type I IFN-regulated genes and proteins. This could affect platelet activation and contribute to development of vascular disease in SLE. In addition, platelets with type I IFN signature could be a novel marker for vascular disease in SLE.
Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease.
Sex, Age, Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance.
Specimen part, Cell line
View SamplesHEK 293 cells were transiently transfected with plasmids expressing Vector only(PCMV), Aire, or MBD-VP16 with the goal of comparing the global gene expression profiles in the Aire and MBD-VP16 groups
The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance.
Specimen part, Cell line
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