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SRP159281
Mus musculus
16 Downloadable Samples
Illumina HiSeq 2000, NextSeq 500
Description
Mutations altering the normal function of C/EBPa are frequent in acute myeloid leukaemia with normal karyotype. MYB, a cooperating partner of C/EBPa, is likewise heavily implicated in AML. Here we investigate how the relative requirement for the transcription factor MYB in AML relates to the particular combinations of wild type and mutated alleles of CEBPA. Through knockdown of Myb in murine cell lines modelling the spectrum of CEBPA mutations we show that the consequences of reduced Myb depend on the mutational status of Cebpa. Importantly, Myb knockdown fails to override the block in myeloid differentiation in cells with biallelic N-terminal C/EBPa mutations, demonstrating for the first time that the dependency on Myb observed in AML is much lower in leukaemia with this combination of mutations. By comparing genome-wide analyses of gene expression following Myb knockdown and ChIP-seq data for the binding of C/EBPa isoforms, we provide evidence for a functional cooperation between C/EBPa and Myb in the maintenance of the leukaemia state. This co-dependency breaks down when both alleles of CEBPA harbour N-terminal mutations, as a subset of C/EBPa-regulated genes only bind the short p30 C/EBPa isoform and, unlike other C/EBPa regulated genes, do so without a requirement for Myb. Overall design: Gene expression analysis of FMH9, KL and LL cells with and without Myb knockdown
Publication Title
Dependence on Myb expression is attenuated in myeloid leukaemia with N-terminal CEBPA mutations.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Ion Torrent Proton
Description
Purpose:To identify resistance mechanisms for the chemotherapeutic drug fludarabine in chronic lymphocytic leukemia (CLL), as innate and acquired resistance to fludarabine-based chemotherapy represents a major challenge for long-term disease control. Methods: We employed piggyBac transposon-mediated mutagenesis, combined with next-generation sequencing, to identify genes that confer resistance to fludarabine in a human CLL cell line. Results: RNA-seq profiling of fludarabine-resistant cells suggested deregulated MAPK signaling as involved in mediating drug resistance in CLL. Overall design: To address if the fludarabine-resistant HG3 cells were transcriptionally different at a global level compared to their parental cells, we performed RNA-sequencing of three pairs of HG3 pools
Publication Title
Transposon Mutagenesis Reveals Fludarabine Resistance Mechanisms in Chronic Lymphocytic Leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 43 Downloadable Samples
Affymetrix Rat Genome U34 Array (rgu34a)
Description
Microarray analysis of parity induced gene expression changes in the mammary glands of four strains of rats to identify a common gene signature associated with protection against methylnitrosourea induced mammary tumorigenesis.
Publication Title
Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of transcription response of undifferentiated human BE(2)-C neuronal cells to stimulation with purified antimycin A1a or unfractionated commercially available antimycin A (Sigma A8674).
Publication Title
Discovery of potent broad spectrum antivirals derived from marine actinobacteria.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of transcription response of undifferentiated human BE(2)-C neuronal cells to stimulation with novel indole-2-carboxamide antivirals 205432 or 206381.
Publication Title
Novel indole-2-carboxamide compounds are potent broad-spectrum antivirals active against western equine encephalitis virus in vivo.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Gene expression profile of primary human CD34+/CD38lo cells differentiating along the megakaryocyte lineage.
Publication Title
Gene expression profile of primary human CD34+CD38lo cells differentiating along the megakaryocyte lineage.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: To analyze the mRNA content of Foxd1Cre;Smo(flox/-) mutant kidneys. Methods: We collected E13.5 wildtype and Foxd1Cre;Smo(flox/-) mutant kidneys and isolated RNA to do RNA-Seq. Results: Identified differentially expressed transcripts in Foxd1Cre;Smo(flox/-) mutant kidneys compared to wildtype controls. Conclusions: Our work provides novel insight into how Hedgehog signaling from stromal cells influences renal development. Overall design: RNA sequencing of Foxd1Cre;Smo(flox/-) mutant kidneys compared to controls.
Publication Title
Hedgehog-GLI signaling in <i>Foxd1-</i>positive stromal cells promotes murine nephrogenesis via TGFβ signaling.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Through development of an in vivo orthotopic lung cancer model, we reveal an unanticipated pathway driving spontaneous metastasis that is orchestrated by the developmentally-regulated transcriptional repressor, Capicua (CIC). Overall design: RNAseq and DNA copy number analysis of H1975 (EGFR-mutant lung adenocarcinoma) cells in the context of drug resistance to rociletinib
Publication Title
Inactivation of Capicua drives cancer metastasis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 86 Downloadable Samples
- IlluminaHiSeq2000
Description
Here we provide fundamental insights into early human development by single-cell RNA-sequencing of human and mouse preimplantation embryos. We elucidate conserved transcriptional programs along with those that are human-specific. Importantly, we validate our RNA-sequencing findings at the protein level, which further reveals differences in human and mouse embryo gene expression. For example, we identify several genes exclusively expressed in the human pluripotent epiblast including the transcription factor KLF17. Key components of the TGF-ß signaling pathway including NODAL, GDF3, TGFBR1/ALK5, LEFTY1, SMAD2, SMAD4 and TDGF1 are also enriched in the human epiblast. Intriguingly, inhibition of TGF-ß signaling abrogates NANOG expression in human epiblast cells, consistent with a requirement for this pathway in pluripotency. Although key trophectoderm factors Id2, Elf5, and Eomes are exclusively localized to this lineage in the mouse, the human orthologues are either absent or expressed in alternative lineages. Importantly, we also identify genes with conserved expression dynamics including Foxa2/FOXA2, which we show is restricted to the primitive endoderm in both human and mouse embryos. Comparisons of the human epiblast to existing embryonic stem cells (hESCs) reveals conservation of pluripotency but also additional pathways more enriched in hESCs. Our analysis highlights significant differences in human preimplantation development compared to mouse and provides a molecular blueprint to understand human embryogenesis and its relationship to stem cells. Overall design: Single-Cell RNA-seq
Publication Title
Defining the three cell lineages of the human blastocyst by single-cell RNA-seq.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To determine gene expression changes during in vitro senescence of MSC we have analyzed differential expression of the corresponding early passage (P2) and senescent passage (PX). There were global changes in the gene expression profile that were reproducible in three independent donor samples.
Publication Title
Replicative senescence of mesenchymal stem cells: a continuous and organized process.
Sample Metadata Fields
No sample metadata fields
View Samples