Hereditary Persistence of Fetal Hemoglobin (HPFH) is characterized by persistent high levels of fetal hemoglobin (HbF) in adults. Several contributory factors, both genetic and environmental, have been identified, but others remain elusive. Ten of twenty-seven members from a Maltese family presented with HPFH. A genome-wide SNP scan followed by linkage analysis revealed a candidate region on chromosome 19p13.12-13. Sequencing identified a nonsense mutation in the KLF1 gene, p.K288X, ablating the DNA binding domain of this key erythroid transcriptional regulator. Only HPFH family members were heterozygote carriers of this mutation. Expression profiling on primary erythroid progenitors revealed down-regulation of KLF1 target genes in HPFH samples. Functional assays demonstrated that, in addition to its established role in adult globin expression, KLF1 is a critical activator of the BCL11A gene, encoding a suppressor of HbF expression. These observations provide a rationale for the effects of KLF1 haploinsufficiency on HbF levels. To identify differentially expressed genes, RNA was isolated from erythroid progenitors (HEPs) cultured from peripheral blood of four HPFH (KLF1 p.K288X/wt) and four non-HPFH family members (wt/wt) and used for genome-wide expression analysis.
Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin.
Specimen part
View SamplesWe studied whether the accumulation of lipids in the fasted kidney are derived from lipoproteins or (non-esterified fatty acids) NEFAs. With overnight fasting, kidneys accumulated triglyceride, but had reduced levels of ceramide and glycosphingolipid species. Fasting led to a nearly 5-fold increase in kidney uptake of plasma [14C]oleic acid. Increasing circulating NEFAs using a ß adrenergic receptor agonist caused a 15-fold greater accumulation of lipid in the kidney, while mice with reduced NEFAs due to adipose tissue deficiency of adipose triglyceride lipase had reduced triglycerides. Cluster of differentiation (Cd)36 mRNA increased 2-fold, and angiopoietin-like 4 (Angptl4), an LPL inhibitor, increased 10-fold. Fasting-induced kidney lipid accumulation was not affected by inhibition of LPL with poloxamer 407 or by use of mice with induced genetic LPL deletion. Despite the increase in CD36 expression with fasting, genetic loss of CD36 did not alter fatty acid uptake or triglyceride accumulation. Our data demonstrate that fasting-induced triglyceride accumulation in the kidney correlates with the plasma concentrations of NEFAs, but is not due to uptake of lipoprotein lipids and does not involve the fatty acid transporter, CD36. Overall design: Mice (n=4-5/group) were either fasted for 16 hours or fed ad libitum. Kidneys were removed and snap frozen. RNA was extracted for sequencing.
Kidney triglyceride accumulation in the fasted mouse is dependent upon serum free fatty acids.
Sex, Cell line, Treatment, Subject
View SamplesThese data include RNA Seq data generated from Ring1b wild type and Ring1b KO Ring1a-/- Cdkn2a-/- Lin- HSC cells non-transduced or transduced with MLL-AF9, HOXA9 and PML-RARa. Overall design: Total RNA extracted from Ring1b wild type and Ring1b KO Ring1a-/- Cdkn2a-/- Lin- HSC cells non-transduced or transduced with MLL-AF9, HOXA9 and PML-RARa.
Maintenance of leukemic cell identity by the activity of the Polycomb complex PRC1 in mice.
No sample metadata fields
View SamplesThese data include RNA Seq data generated from wild type and Ring1a Ring1b dKO Cdkn2a-/- MLL-AF9 Leukemic cells Overall design: mRNA library preparation from Ring1a-/-;Ring1bf/f Cdkn2a-/- MLL-AF9 leukemic cells treated with OHT or EtOH
Maintenance of leukemic cell identity by the activity of the Polycomb complex PRC1 in mice.
Cell line, Treatment, Subject
View SamplesSca1+/cKit hematopoietic BMCs of hosts bearing primary tumors promote the growth of distant tumors that form with a myofibroblast-rich, desmoplastic stroma. BMCs from old mice bearing primary tumors lack this ability
Hematopoietic Age at Onset of Triple-Negative Breast Cancer Dictates Disease Aggressiveness and Progression.
Sex, Specimen part
View SamplesTo examine the effects of recombinant granulin on human mammary stromal fibroblasts, we cultured immortalized GFP+ normal human mammary fibroblasts in the presence of recombinant human granulin (1ug/ml) or PBS every 24h for 6 days. To generate GRN-independent CAFs, we injected immortalized GFP+ human mammary fibroblasts, MCF7Ras human breast carcinoma cells, and 20% Matrigel subcutaneously into nude mice. Tumors were allowed to form for a period of 45 days. GFP+ fibroblasts were isolated from tumors by mincing the tumors, dissociating, and culturing in the presence of 1 ug/ml puromycin for ~3-4 weeks. CAF purity was confirmed by ensuring that 100% of the population was GFP-positive.
Hematopoietic Age at Onset of Triple-Negative Breast Cancer Dictates Disease Aggressiveness and Progression.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to chromatin in embryonic stem cells.
Specimen part
View SamplesO-linked N-acetylglucosamine (O-GlcNAc ) transferase (OGT) activity is essential for embryonic stem (ES) cell viability and mouse development. OGT is present in both cytoplasm and nucleus of different cell types and mediates serine or threonine glycosylation. The Ogt gene locus resides on the X-chromosome and its activity is required for the viability of male ES cells. Using Ogt conditional knock out (KO) ES cells it was shown the failure of establishing stable KO ES clones further suggesting that Ogt activity is required for ES cell self-renewal and pluripotency. For understanding these changes, we performed global gene expression upon silencing of Ogt mediated by esiRNA in mouse Embryonic Stem Cells.
Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to chromatin in embryonic stem cells.
Specimen part
View SamplesPolycomb proteins control proliferation and cellular transformation regulating DNA replication independently of cell cycle checkpoints
Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication.
Specimen part
View SamplesRNA-Sequencing (RNA-seq). The aim of this RNA-seq experiment was to monitor the genome-wide transcriptional changes in mouse embryonic stem cells depleted of either Fam60a or Sin3a. Overall design: RNA-Seq of mRNA level of mESCs depleted for Sin3a and Fam60a.
Fam60a defines a variant Sin3a-Hdac complex in embryonic stem cells required for self-renewal.
Specimen part, Subject
View Samples