Filters
Technology
Platform
GSE49938
Homo sapiens
28 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human pluripotent stem cells were differentiated into hematopoietic progenitors, which were then re-specified using defined transcription factors to resemble hematopoietic stem cells (HSC)
Publication Title
Induction of multipotential hematopoietic progenitors from human pluripotent stem cells via respecification of lineage-restricted precursors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The PLZF-RARa fusion oncoprotein is overexpressed in the t(11;17) subtype of acute promyelocytic leukemia. Gene expression microarrays were used to identify genes involved in leukemic transformation.
Publication Title
Comprehensive genomic screens identify a role for PLZF-RARalpha as a positive regulator of cell proliferation via direct regulation of c-MYC.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
NextSeq 500
Description
We performed morphogen-directed differentiation of human PSCs into HE followed by combinatorial screening of 26 candidate HSC-specifying TFs for the potential to promote hematopoietic engraftment in irradiated immune deficient murine hosts. We recovered seven TFs (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1, SPI1) that together were sufficient to convert HE into hematopoietic stem and progenitor cells (HSPCs) that engraft primary and secondary murine recipients Overall design: Examination of expression pattern in hematopoietic cells.
Publication Title
Haematopoietic stem and progenitor cells from human pluripotent stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
While gene expression dynamics have been extensively catalogued during hematopoietic differentiation in the adult, less is known about transcriptome diversity of human hematopoietic stem cells (HSCs) during development. To characterize transcriptional and post-transcriptional changes in HSCs during development, we leveraged high-throughput genomic approaches to profile miRNAs, lincRNAs, and mRNAs. Our findings indicate that HSCs manifest distinct alternative splicing patterns in key hematopoietic regulators. Detailed analysis of the splicing dynamics and function of one such regulator, HMGA2, identified an alternative isoform that escapes miRNA-mediated targeting. We further identified the splicing kinase CLK3 that, by regulating HMGA2 splicing, preserves HMGA2 function in the setting of an increase in let-7 miRNA levels, delineating how CLK3 and HMGA2 form a functional axis that influences HSC properties during development. Collectively, our study highlights molecular mechanisms by which alternative splicing and miRNA-mediated post-transcriptional regulation impact the molecular identity and stage-specific developmental features of human HSCs. Overall design: RNA-seq of HPC-5F cells transduced with a control (CTRL), HMGA2-L (LONG), HMGA2-S (SHORT) or CLK3 ORF lentiviral over-expression vectors.
Publication Title
A CLK3-HMGA2 Alternative Splicing Axis Impacts Human Hematopoietic Stem Cell Molecular Identity throughout Development.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients. Reprogrammed DBA progenitors recapitulate defects in erythroid differentiation which were rescued by gene complementation. Unbiased chemical screens identified SMER28, a small molecule inducer of autophagy, which enhanced erythropoiesis in a range of in vitro and in vivo models of DBA. SMER28 acted through autophagy factor ATG5 to stimulate erythropoiesis and upregulate expression of globin genes. These findings present an unbiased drug screen for hematological disease using iPSCs and identify autophagy as a therapeutic pathway in DBA.
Publication Title
Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors.
Sample Metadata Fields
Treatment
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Intrauterine growth restriction is a common complication of pregnancy. We induce IUGR in rats by bilateral uterine artery ligation at e18 of a 23 day gestation.
Publication Title
Neutralizing Th2 inflammation in neonatal islets prevents β-cell failure in adult IUGR rats.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2500
Description
HeLa cells lacking MORC2 generated through CRISPR/Cas9-mediated gene disruption were reconstituted with either wild-type or R252W mutant MORC2, and re-repression of HUSH target genes assessed by RNA-seq Overall design: Total RNA-seq of MORC2 knockout cells, either 1) mock transduced, 2) transduced with lentiviral vector encoding wild-type MORC2 or 3) transduced with lentviral vector encoding R252W MORC2.
Publication Title
Hyperactivation of HUSH complex function by Charcot-Marie-Tooth disease mutation in MORC2.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 270 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Acute lymphoblastic leukaemia with early T-cell precursor immunophenotype (ETP ALL) is a highly aggressive subtype of ALL of unknown aetiology. To gain insights into the genetic basis of this disease, we performed whole genome sequencing of tumour and normal DNA of 12 children with ETP ALL. Analysis of structural and sequence variants in this discovery cohort, and mutation recurrence screening in a panel of 51 ETP and 43 non ETP ALL samples identified a high frequency of activating mutations in genes regulating cytokine receptor and Ras signalling, including IL7R, NRAS, KRAS, FLT3, BRAF, JAK1 and JAK3 in ETP ALL. Moreover, we identified multiple new targets of mutation in including GATA3, EP300, RUNX1, DNM2, ECT2L, HNRNPA1 and HNRNPR, as well as genes known to be mutated in T-ALL, including NOTCH1, PHF6, and WT1.. Five of 12 ETP ALL cases harboured novel chromosomal translocations, several of which accompanied complex multichromosomal rearrangements and resulted in the expression of chimeric in-frame fusion genes disrupting hematopoietic regulators, including ETV6-INO80D, NAP1L1-MLLT10 and RUNX1-EVX1. These results indicate that although ETP ALL is genetically heterogeneous, activation of Ras and cytokine receptor signalling distinguishes this disease from non-ETP ALL. These findings suggest that targeting this pathway may improve the currently dismal outcome of this disease.
Publication Title
The genetic basis of early T-cell precursor acute lymphoblastic leukaemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 50 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole genome sequencing of tumour and normal DNA from 12 children with ETP ALL and assessed the frequency of somatic alterations in 52 ETP and 42 non-ETP T-ALL samples by sequencing and DNA copy number analysis. ETP ALL was characterised by a high frequency of activating mutations in genes regulating cytokine receptor and Ras signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF); alterations disrupting haemopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1, EP300); and inactivating mutations in histone modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of mutation including DNM2, ECT2L and RELN. Ten of 12 ETP ALL cases harboured chromosomal rearrangements, several of which complex and resulted in the expression of novel chimeric in-frame fusion genes disrupting haemopoietic regulators. Thus, similar to myeloid malignancies, mutations that drive proliferation, impair differentiation and disrupt histone modification are hallmarks of ETP ALL. Moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haemopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.
Publication Title
The genetic basis of early T-cell precursor acute lymphoblastic leukaemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 107 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Comparative analysis can provide important insights into complex biological systems. As demonstrated in the accompanying paper, Translating Ribosome Affinity Purification (TRAP), permits comprehensive studies of translated mRNAs in genetically defined cell populations following physiological perturbations.
Publication Title
Application of a translational profiling approach for the comparative analysis of CNS cell types.
Sample Metadata Fields
No sample metadata fields
View Samples