Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA260506 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:7-dehydrocholesterol reductase catalyzes the reduction of 7-dehydrocholesterol to cholesterol. In Smith-Lemli-Opitz syndrome, mutations in DHCR7 prevents this conversion. We have found iPS cells derived from SLOS patients exhibit accelerated differentiation under cholesterol poor conditions. In this dataset, we include expression data obtained from comparision of a control iPS cell line (BJ) and a SLOS iPS cell line (A2). Cell line gene expression was compared in cholesterol rich conditions where the SLOS phenotype is suppressed. Cholesterol deficient culture of control and SLOS iPS cells demonstrated enhanced differentiation of SLOS cells over 7 days. These data are used to obtain 308 genes that are differentially expressed upon cholesterol deficient culture. time-course expression data obtained from control and SLOS patient iPS cells after transfer from cholesterol rich to cholesterol deficient culture.
2015-09-18 | GSE61203 | GEO
Project description:7-dehydrocholesterol reductase catalyzes the reduction of 7-dehydrocholesterol to cholesterol. In Smith-Lemli-Opitz syndrome, mutations in DHCR7 prevents this conversion. We have found iPS cells derived from SLOS patients exhibit accelerated differentiation under cholesterol poor conditions. In this dataset, we include expression data obtained from comparision of a control iPS cell line (BJ) and a SLOS iPS cell line (A2). Cell line gene expression was compared in cholesterol rich conditions where the SLOS phenotype is suppressed. Cholesterol deficient culture of control and SLOS iPS cells demonstrated enhanced differentiation of SLOS cells over 7 days. These data are used to obtain 308 genes that are differentially expressed upon cholesterol deficient culture. time-course expression data obtained from control and SLOS patient iPS cells after transfer from cholesterol rich to cholesterol deficient culture. 48 total RNA samples were isolated and hybridized on Affymetrix arrays. We generated the following pairwise comparisons using Partek: BJ 0hr vs A2 0hr; BJ 2Day vs A2 2Day; BJ 3Day vs A2 3Day; BJ 4Day vs A2 4Day; BJ 5Day vs A2 5Day; BJ 7Day vs A2 7Day. Genes with an FDR≤10% and a fold-change ≥3 were identified as significantly different. We also performed pairwise comparison of BJ and A2 samples within each cell line between subsequent isolations (i.e. BJ 0hr vs BJ 2Day; A2 3Day vs A2 4Day; etc.)
2015-09-18 | E-GEOD-61203 | biostudies-arrayexpress
Project description:Fanconi anemia (FA) is a genetic disorder of DNA repair that manifests as bone marrow dysfunction typically occurring in childhood. The lack of human model systems has impeded progress in identifying effective therapies. To address this, efforts have focused on using directed differentiation of patient-derived human induced pluripotent stem cells (IPSCs) to hematopoietic stem and progenitor cells (HSPCs). However, the requirement for an intact FA DNA repair pathway for efficient reprogramming of patient cells to pluripotency requires genetic complementation of FA pathway defects to efficiently generate IPSCs, precluding derivation of FA pathway-deficient human HSPCs for study. To overcome this barrier, we employed a system of doxycycline-inducible complementation of FANCA deficient patient-derived IPS cells. Doxycycline exposure allowed for the robust maintenance of undifferentiated IPS cells in culture. Removal or retention of doxycycline exposure during directed differentiation of HSPCs allowed for the production of isogenic FANCA-deficient and FANCA-complemented human HSPCs. IPS-derived, FANCA-deficient HSPCs showed impaired response to genotoxic stress, proliferation, and survival compared to complemented HSPCs. Using these cells, we found that FANCA-deficient HSPCs showed expected impaired clonogenicity in methylcellulose culture and unexpected accelerated erythroid differentiation relative to complemented cells. Activation of p53-mediated p21 transactivation in FANCA-deficient HSPCs serves to drive accelerated erythropoiesis as the expense of clonogenicity. This study demonstrates the feasibility of inducible complementation in IPSCs as a method to generate isogenic FA-deficient and FA-complemented human HPSCs for disease modeling and uncovers a novel mechanism by which the FA pathway regulates the balance between stem cell maintenance and terminal differentiation.
2021-02-01 | GSE123194 | GEO
Project description:The 22q11.2 deletion syndrome (22q11.2DS) is the most common copy number variant (CNV)-associated syndrome, leading to congenital and neuropsychiatric anomalies. Patient-derived, induced pluripotent stem cell (iPS) models have provided important insight into the mechanisms of phenotypic features of this condition. However, patient-derived iPSC models may harbor underlying genetic heterogeneity that can confound analysis of pathogenic CNV effects. Furthermore, the ~1.5 Mb “A-B” deletion at this locus is inherited at higher frequency than the more common ~2.7 Mb “A-D” deletion, but remains under-studied due to lack of relevant models. To address these issues, here we leveraged a CRISPR-based strategy in Cas9-expressing iPS cells to engineer novel isogenic models of the 22q11.2 “A-B” deletion. After in vitro differentiation to excitatory neurons, integrated transcriptomic and cell surface proteomics identified deletion-associated alterations in surface adhesion markers. Furthermore, implantation of iPS-derived neuronal progenitor cells into the cortex of neonatal mice found decreased proliferation and accelerated neuronal maturation within a relevant microenvironment. Taken together, our results suggest potential pathogenic mechanisms of the 22q11.2 “A-B” deletion in driving neuronal and neurodevelopmental phenotypes. We further propose that the isogenic models generated here will provide a unique resource to study this less-common variant of the 22q11.2 microdeletion syndrome.
2023-05-11 | PXD032075 | Pride
Project description:We performed single-cell sequencing to characterize the cell types that are present in human induced pluripotent stem cell derived (iPS) kidney organoids and their transcriptional profile. Furthermore, using bulk RNA sequencing we compared the transcriptional profile of kidney organoid derived podocytes from a wildtype iPS line, an iPS line with 2 mutations in podocin (NPHS2) which causes clinical manifestation of nephrotic syndrome and an iPS line with one of these mutations repaired which causes no clinical symptoms. For reference and comparison we took along human in vivo glomeruli and a human conditionally immortalized podocyte cell line.
2022-04-25 | GSE181954 | GEO
Project description:We used heterokaryon cell fusion based reprogramming and identified the cytokine IL6 as a potential regulator of reprogramming to pluripotency. We generated iPS clones using the four reprogramming factors (4F) Oct4, Klf4, Sox2, and c-Myc. In addition, iPS clones were generated using only three factors (3F: Oct4, Klf4, amd Sox2) with the addition of the cytokine IL6 to reprogramming culture conditions. Global RNA-Seq of the 3F + IL6 derived iPS clones was done for comparison with 4F-derived iPS clones, mouse embryonic stem cells and mouse embryonic fibroblasts.
2013-08-28 | GSE46104 | GEO
Project description:Human induced pluripotent stem (iPS) cells derived from somatic cells of patients hold great promise for modelling human diseases. Dermal fibroblasts are frequently used for reprogramming, but require an invasive skin biopsy and a prolonged period of expansion in cell culture prior to use. Here, we report the derivation of iPS cells from multiple human blood sources including peripheral blood mononuclear cells (PBMCs) harvested by routine venipuncture. Peripheral blood-derived human iPS lines are comparable to human embryonic stem (ES) cells with respect to morphology, expression of surface antigens, activation of endogenous pluripotency genes, DNA methylation and differentiation potential. Analysis of Immunoglobulin and T-cell receptor gene rearrangement revealed that some of the PBMC iPS cells were derived from T-cells, documenting derivation of iPS cells from terminally differentiated cell types. Importantly, peripheral blood cells can be isolated with minimal risk to the donor and can be obtained in sufficient numbers to enable reprogramming without the need for prolonged expansion in culture. Reprogramming from blood cells thus represents a fast, safe and efficient way of generating patient-specific iPS cells.
2010-06-10 | GSE22167 | GEO
Project description:Pluripotency, the capacity of embryo-derived stem cells to generate all tissues in the organism, can be induced in somatic cells by nuclear transfer into oocyte, fusion with embryonic stem cells, and for male germ cells by cell culture alone. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors (Oct4, Sox2, Klf4, and Myc) to yield induced Pluripotent Stem (iPS) cells. Using the same four factors, we have derived iPS cells from human embryonic stem cell-derived fibroblasts, primary human fetal cells, and diverse cells of neonatal and adult human origin. The human iPS cells manifest the colony morphology, gene expression patterns, and epigenetic characteristics of human Embryonic Stem (hES) cells, and form well-differentiated teratomas in immune-deficient mice. These data demonstrate that defined factors can reprogram human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture. Biological replicates:; GSM248201 and GSM248202; GSM248205 and GSM248206; GSM248207 and GSM248208; GSM248209 and GSM248210; GSM248211 and GSM248212; GSM248213 and GSM248214. Sample descriptions:; H1-OGN: ES cells expressing GFP-NEO marker under OCT4 promoter; dH1f: differentiated H1-OGN fibroblasts; dHcf16: differentiated H1-OGN cloned fibroblasts; MRC5: fetal lung fibroblasts; BJ1: neonatal fibroblasts Experiment Overall Design: RNA samples from hES cells, differentiated hES cells, human fibroblasts, iPS cells from differentiated hES cells, and iPS cells from human fibroblasts. Gene expression of those cells were analyzed.
2008-06-17 | E-GEOD-9832 | biostudies-arrayexpress
Project description:Pluripotency, the capacity of embryo-derived stem cells to generate all tissues in the organism, can be induced in somatic cells by nuclear transfer into oocyte, fusion with embryonic stem cells, and for male germ cells by cell culture alone. Recently, murine fibroblasts have been reprogrammed directly to pluripotency by ectopic expression of four transcription factors (Oct4, Sox2, Klf4, and Myc) to yield induced Pluripotent Stem (iPS) cells. Using the same four factors, we have derived iPS cells from human embryonic stem cell-derived fibroblasts, primary human fetal cells, and diverse cells of neonatal and adult human origin. The human iPS cells manifest the colony morphology, gene expression patterns, and epigenetic characteristics of human Embryonic Stem (hES) cells, and form well-differentiated teratomas in immune-deficient mice. These data demonstrate that defined factors can reprogram human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture. Biological replicates: GSM248201 and GSM248202; GSM248205 and GSM248206; GSM248207 and GSM248208; GSM248209 and GSM248210; GSM248211 and GSM248212; GSM248213 and GSM248214. Sample descriptions: H1-OGN: ES cells expressing GFP-NEO marker under OCT4 promoter dH1f: differentiated H1-OGN fibroblasts dHcf16: differentiated H1-OGN cloned fibroblasts MRC5: fetal lung fibroblasts BJ1: neonatal fibroblasts Keywords: cellular reprogramming
2007-12-10 | GSE9832 | GEO
Project description:Genome instability is a potential limitation to the research and therapeutic application of induced pluripotent stem cells (iPSCs). Observed genomic variations reflect the combined activities of DNA damage, cellular DNA damage response (DDR), and selection pressure in culture. To understand the contribution of DDR on the distribution of copy number variations (CNVs) in iPSCs, we mapped CNVs of iPSCs with mutations in the central DDR gene ATM onto genome organization landscapes defined by genome-wide replication timing profiles. We show that following reprogramming the early and late replicating genome is differentially affected by CNVs in ATM deficient iPSCs relative to wild type iPSCs. Specifically, the early replicating regions had increased CNV losses during retroviral reprogramming. This differential CNV distribution was not present after later passage or after episomal reprogramming. Comparison of different reprogramming methods in the setting of defective DNA damage response reveals unique vulnerability of early replicating open chromatin to retroviral vectors. We isolated RNA from Ataxia-telangiectasia (A-T) patient fibroblast derived iPS cells and A-T patient fibroblasts for hybridization to the Affymetrix gene expression microarrays.
2016-03-29 | E-GEOD-78716 | biostudies-arrayexpress