Individuals with Trisomy 21 (T21) exhibit numerous hematological abnormalities, including reductions in numbers of circulating B and T lymphocytes. To elucidate molecular mechanisms underlying these phenotypes, we differentiated human isogenic disomic and trisomic pluripotent cells, and observed that trisomic cells showed defects in B cell, but not T, cell differentiation. Global gene expression of differentiated, trisomic B cells revealed reduced expression of genes encoding endothelin signaling components, namely the Endothelin Receptor B (Ednrb), and its ligand Endothelin1 (Edn1).. Depletion of Ednrb mRNA in cord blood CD34+ cells led to defective B cell differentiation, supporting an hypothesis that low expression of Ednrb in T21 contributes to intrinsic lymphoid defects. Further evidence for the role of the Ednrb pathway in B cell differentiation was obtained through CRISPR/Cas9 gene targeting in disomic and trisomic iPS cells. Knockout of Ednrb in both cell backgrounds reduced the capacity for B cell differentiation. Collectively, this work identifies downregulation of Ednrb as a causative factor for impaired B lymphocyte generation in trisomic cells, which may contribute to defects in immune function associated with T21. Furthermore, a novel role for endothelin signaling in regulation of B cell development has been identified.
Downregulation of Endothelin Receptor B Contributes to Defective B Cell Lymphopoiesis in Trisomy 21 Pluripotent Stem Cells.
Specimen part
View SamplesUsing UNC0638 and genetic assays to inhibit EHMT1/2 and derepress fetal hemoglobin in adult hematopoietic cells. Overall design: RNA-Seq in primary adult human erythroid cells treated with UNC0638 or the vehicle control (DMSO) in biological triplicates.
EHMT1 and EHMT2 inhibition induces fetal hemoglobin expression.
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View SamplesANGPTL2 is a protein in the angiopoietin-like protein family and plays a role in hematopoietic and vascular physiology. This study examined the effects of ANGPTL2 on CD34+ human hematopoetic progenitor cells.
Angiopoietin-like proteins stimulate HSPC development through interaction with notch receptor signaling.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells.
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View SamplesEGR3 expression is upregulated in human prostate cancer compared to normal prostate tissue and is associated with absence of relapse, while low EGR3 expression in tumors is predicitive of disease relapse (Pio et al., PLOS One 2013; 8(1):e54096). However the function of EGR3 in prostate cancer is unknown. Human prostate cancer cells M12 containing high levels of EGR3 were used for shRNA-mediated silencing of EGR3. Gene expression analysis of EGR3 knockdown cells reveals a role in inflammation and the existence of a crosstalk with the NFkB pathway.
Early growth response 3 (Egr3) is highly over-expressed in non-relapsing prostate cancer but not in relapsing prostate cancer.
Cell line, Treatment
View SamplesThe anthracycline, doxorubicin (Dox), is widely used in oncology, but it may it may cause a cardiomyopathy which has dismal prognosis and cannot be effectively prevented. The secretome of multipotent human amniotic fluid-derived stem cells (hAFS) has previously been demonstrated to reduce ischemic cardiac damage. Here, it is shown that the hAFS conditioned medium (hAFS-CM) antagonizes senescence and apoptosis of cardiomyocytes and cardiac progenitor cells, two major features of Dox cardiotoxicity. Mechanistic studies with primary mouse neonatal cardiomyocytes reveal that hAFS-CM inhibition of Dox-elicited senescence and apoptosis is paralleled by decreased DNA damage and is associated with nuclear translocation of NF-kB and upregulation of a set of genes controlled by NF-kB, namely Il6 and Cxcl1, which promote cardiomyocyte survival, and Cyp1b1 and Abcb1, which encode for proteins involved in Dox metabolism and efflux, respectively. The PI3K/Akt signaling cascade, upstream of NF-kB, is potently activated by the hAFS-CM and pre-treatment with a PI3K inhibitor abrogates NF-kB accumulation into the nucleus, modulation of its target genes, and prevention of Dox-initiated senescence and apoptosis in response to the hAFS-CM. This work may lay the ground for the development of a stem cell-based paracrine therapy of chemotherapy-related cardiotoxicity.
The human amniotic fluid stem cell secretome effectively counteracts doxorubicin-induced cardiotoxicity.
Specimen part
View SamplesTo examine the molecular phenotype of hypoxic cardiomyocytes in their native environment, we isolated tdTomato+ cardiomyocytes from fresh cryosections using laser microdissection. And perform gene expression analysis using RNA sequencing (RNA-seq).
Hypoxia fate mapping identifies cycling cardiomyocytes in the adult heart.
No sample metadata fields
View SamplesDepending on the tumor type IB kinase (IKK) can act as tumor promoter or tumor suppressor in various malignancies. Here we demonstrate a key function of IKK in the suppression of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKK kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of IFN expressing M1-like myeloid cells. In IKK mutant mice M1-like polarization is not controlled in a cell autonomous manner but depends rather on the interplay of both IKK mutant tumor epithelia and immune cells.
IKKα promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells.
Specimen part, Time
View SamplesPlants of Arabidopsis thaliana (ecotype Col-0, nrb4-2 and nrb4-4) were grown in phytochambers in short day conditions during three weeks. Then, samples from different pots were mixed, and the RNA extracted.
Non-recognition-of-BTH4, an Arabidopsis mediator subunit homolog, is necessary for development and response to salicylic acid.
Age
View SamplesPrimordial germ cells (PGCs), the embryonic precursors of eggs and sperm, are a unique model for identifying and studying regulatory mechanisms in singly migrating cells. From their time of specification to eventual colonization of the gonad, mouse PGCs traverse through and interact with many different cell types, including epithelial cells and mesenchymal tissues. Work in drosophila and zebrafish have identified many genes and signaling pathways involved in PGC migration, but little is known about this process in mammals.
Discrete somatic niches coordinate proliferation and migration of primordial germ cells via Wnt signaling.
Specimen part
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