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SRP137147
Homo sapiens
149 Downloadable Samples
Description
Megakaryocytic-Erythroid Progenitors (MEP) produce circulating red blood cells and platelets. Although much is known regarding megakaryocytic (Mk) and erythroid (E) maturation, detailed molecular mechanisms underlying the MEP fate decision have not been determined. Single cell RNA sequencing of highly enriched populations of primary human common myeloid progenitors (CMP), MEP, megakaryocyte progenitors (MKP) and erythroid progenitors (ERP), revealed that MEP have a distinct molecular signature with co-expression of genes otherwise expressed exclusively in CMP, MKP or ERP. Cell cycle genes are significantly differentially expressed between MEP, MKP, and ERP. We therefore tested the effects on MEP fate of genetic and pharmacologic modulation of cell cycle progression, and found that cell cycle activity mechanistically controls MEP fate decisions; cell cycle activation promotes E whereas cell cycle inhibition promotes Mk specification. The data obtained from healthy cells can now be applied to the mechanisms underlying benign and malignant disease states of Mk and E production. Overall design: To address the heterogeneity of the MEP enriched population, we performed single-cell mRNA sequencing (scRNA-seq) of FACS-enriched MEP, MKP and ERP, and CMP. Specifically, we tested whether MEP have an expression signature that is distinct from CMP, MKP and ERP. Single cells were captured and lysed using the Fluidigm C1 platform and sequenced to more accurately identify and profile the transcriptome of multi-lineage cells. On average, there were 504,984 aligned reads per cell, with an average of 5,028 genes expressed (FPKM>0.1) per cell. We first performed an analysis of the scRNA-seq data from sorted CMP, MEP, MKP and ERP populations from a single PBSC donor (donor-1, n=246 cells). Unsupervised analysis with the recently described ICGS software identified separate major gene expression clusters for each of the sorted populations along with subdivisions of the CMP, MEP, MKP and ERP. To confirm the major gene expression clusters associated with the four sorted populations, we performed scRNA-Seq analysis of cells from a different donor (donor-2, n=294 cells) sorted using a complementary gating strategy, but running 1 plate of MEPs and 1 plate of a mix of 55% MKP and 45% ERP.
Publication Title
The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Persistent colonization of the gastric mucosa by Helicobacter pylori (Hp) elicits chronic inflammation and aberrant epithelial cell proliferation, which increases the risk of gastric cancer. We examined the ability of microRNAs to modulate gastric cell proliferation in response to persistent Hp infection and found that epigenetic silencing of miR-210 plays a key role in gastric disease progression. Importantly, DNA methylation of the miR-210 gene was increased in Hp-positive human gastric biopsies as compared to Hp-negative controls. Moreover silencing of miR-210 in gastric epithelial cells promoted proliferation. We identified STMN1 and DIMT1 as miR-210 target genes and demonstrated that inhibition of miR-210 expression augmented cell proliferation by activating STMN1 and DIMT1. Together, our results highlight inflammation-induced epigenetic silencing of miR-210 as a mechanism of induction of chronic gastric diseases, including cancer, during Hp infection.
Publication Title
Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
TET2 is an enzyme for converting methylcytosine (mC) to hydorxymethylcytosine (hmC) and its mutations have been frequently found in myeloid malignancies and T-cell lymphoma in humans. We analyzed Tet2 gene trap mice and found that homozygous mice developed T-cell lymphoma with follicular helper T-cell-like features.
Publication Title
Reduced TET2 function leads to T-cell lymphoma with follicular helper T-cell-like features in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 129 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The gastrointestinal (GI) tract can have significant impact on the regulation of the whole body metabolism and may contribute to the development of obesity and diabetes. To systemically elucidate the role of the GI tract in obesity, we performed a transcriptomic analyses in different parts of the GI tract of two obese mouse models: ob/ob and high-fat diet (HFD) fed mice. Compared to their lean controls, both obese mouse groups had significant amount of gene expression changes in the stomach (ob/ob: 959; HFD: 542), much more than the number of changes in the intestine. Despite the difference in genetic background, the two mouse models shared 296 similar gene expression changes in the stomach. Among those genes, some had known associations to obesity, diabetes and insulin resistance. In addition, the gene expression profile strongly suggested an increased gastric acid secretion in both obese mouse models, probably through an activation of the gastrin pathway. In conclusion, our data reveal a previously unknown dominant connection between the stomach and obesity.
Publication Title
Significant obesity-associated gene expression changes occur in the stomach but not intestines in obese mice.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 45 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Time and dose related expression profiles of rat right heart tissue in microsphere bead model for Pulmonary embolism
Publication Title
Transcriptional profile of right ventricular tissue during acute pulmonary embolism in rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Chromosomal translocation t(8;21) (q22;q22) leading to generation of oncogenic RUNX1-RUNX1T1 (AML1-ETO) fusion is a cytogenetic abnormality observed in about 10% of acute myelogenous leukemia (AML). To uncover somatic mutations that cooperate with t(8;21)-driven leukemia, we performed targeted and whole exome sequencing of newly-diagnosed and relapsed AML samples. We identified high frequency of truncating alterations in ASXL2 along with recurrent mutations of KIT, TET2, MGA, FLT3, and DHX15 in this subtype of AML. To investigate in-depth the role of ASXL2 in normal and malignant hematopoiesis, we utilized a mouse model of ASXL2 deficiency. Loss of ASXL2 caused progressive hematopoietic defects characterized by myeloid cell expansion, splenomegaly, extramedullary hematopoiesis and poor reconstitution ability in transplantation models. A parallel analysis of young and >1-year old Asxl2-deficient mice revealed age-dependent changes in the hematopoietic compartment leading to perturbations affecting not only myeloid and erythroid differentiation but also maturation of lymphoid cells. Our studies also suggest that expression of truncated ASXL2 protein confers proliferative advantage to mouse myeloid progenitors. Overall, these findings establish a critical role of ASXL2 in maintaining steady state hematopoiesis and provide insights into how its loss/mutation primes leukemic growth of myeloid cells. Overall design: Bone marrow derived LSK cells from young (8-12 weeks old) and >1-year old Asxl2 WT and knockout mice were analyzed for gene expression changes.
Publication Title
ASXL2 regulates hematopoiesis in mice and its deficiency promotes myeloid expansion.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
BACKGROUND: p53 is an important tumor suppressor with a known role in the later stages of colorectal cancer, but its relevance to the early stages of neoplastic initiation remains somewhat unclear. Although p53-dependent regulation of Wnt signalling activity is known to occur, the importance of these regulatory mechanisms during the early stages of intestinal neoplasia has not been demonstrated.
Publication Title
A limited role for p53 in modulating the immediate phenotype of Apc loss in the intestine.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
To characterize how symbiotic bacteria affect the lolecular and cellular mechanisms of epithelial homeostasis, human colonic Caco-2 cells
Publication Title
Epithelial cell proliferation arrest induced by lactate and acetate from Lactobacillus casei and Bifidobacterium breve.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Illumina Genome Analyzer II
Description
Backgropund:In a major paradigm shift in the last decade, the knowledge about a whole class of non-coding RNAs known as miRNAs has emerged, which have proved these to be important regulators of a wide range of cellular processes by the way of modulation of gene expression. It is reported that some of these miRNAs are modified by addition or deletion of nucleotides at their ends, after biogenesis. However, the biogenesis and functions of these modifications are not well studied in eukaryotes, especially in plants. In this study, we examined the miRNA modifications in different tissues of the various plants, namely rice, tomato and Arabidopsis and identified some common features of such modifications. Results:We have analyzed different aspects of miRNA modifications in plants. To achieve this end, we developed a PERL script to find the modifications in the sequences using small RNA deep sequencing data. The modification occurs in both mature and passenger (star) strands, as well as at both the 5'' and 3'' ends of miRNAs. Interestingly, we found a position-specific nucleotide biased modification, as evident by increased number of modification at the 5'' end with the presence of Cytosine (nucleotide ''C'') at the 3’end of the miRNA sequence. The level of modifications is not strictly dependent on the abundance of miRNA. Our study showed that the modification events are independent of plant species, tissue and physiological conditions. Our analysis also indicates that the RNAi enzyme, namely, the RNA dependent RNA polymerase 6 (RDR6) may not have any role in Arabidopsis miRNA modifications. Some of these modified miRNAs are bound to AGO1, suggesting their possible roles in biological processes. Conclusions:This is a first report that reveals that 5'' nucleotide additions are preferred for mature miRNA sequences with 3’ terminal ‘C’ nucleotide. Our analysis also indicates that the miRNAs modifications involving addition of nucleotides to the 5’ or 3’ end are independent of RDR6 activity and are not restricted by plant species, physiological conditions and tissue types. The results also indicate that such modifications might be important for biological processes. Overall design: small RNA profiles of wild type and RDR6 (-) of Arabidopsis plants were generated using deep sequencing data.
Publication Title
3' and 5' microRNA-end post-biogenesis modifications in plant transcriptomes: Evidences from small RNA next generation sequencing data analysis.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
We performed an RNA-Seq analysis comparing thymic lymphoma tissues from the p53-null(n=2) and ?Np63?/?;p53-/- (n=3) or ?Np73?/?;p53-/-(n=3). Mice at 10 weeks of age were injected with either Ad-mCherry or Ad-CRE-mCherry to delete ?Np63/?Np73 in the thymic lmyphomas. We aimed to test by deleting the DNp63/DNp73 in these p53-deficient tumors will mediate tumor regression and analyze the expression profile of the genes Overall design: Examination of thymic lymphoma tissues in 3 different genotypes (p53-/- vs ?Np63?/?;p53-/- or ?Np73?/?;p53-/-)
Publication Title
IAPP-driven metabolic reprogramming induces regression of p53-deficient tumours in vivo.
Sample Metadata Fields
No sample metadata fields
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