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SRP083323
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2000
Description
The Hematopoietically-expressed homeobox transcription factor (Hhex) is important for the maturation of definitive hematopoietic progenitors and B-cells during development. We have recently shown that in adult hematopoiesis, Hhex is dispensable for maintenance of hematopoietic stem cells (HSCs) and myeloid lineages but essential for the commitment of Common Lymphoid Progenitors (CLPs) to lymphoid lineages. However, whether Hhex plays a role in HSC self-renewal and myeloid expansion during hematopoietic stress is unknown. Here we show that during serial bone marrow transplantation, Hhex-deleted HSCs are progressively lost, revealing an intrinsic defect in HSC self-renewal. Moreover, Hhex-deleted mice show markedly impaired hematopoietic recovery following myeloablation. In vitro, Hhex-null blast colonies were incapable of replating, implying a specific requirement for Hhex in immature hematopoietic progenitors. Transcriptome analysis of Hhex-null Lin-Sca+Kit+ (LSK) cells showed that Hhex deletion leads to the deregulation of Polycomb Repressive Complex 2 (PRC2) target genes, including an upregulation of Cdkn2a locus, encoding the cell cycle repressors p16Ink4a and p19Arf. Indeed, loss of Cdkn2a restored Hhex-null blast colony replating in vitro, as well as hematopoietic reconstitution following myeloablation in vivo. Thus, HSCs require Hhex to repress Cdkn2a to enable continued self-renewal and response to hematopoietic stress. Overall design: Transcriptional profiling of Hhex-deleted and wild-type LSK cells using RNA sequencing
Publication Title
Hhex Regulates Hematopoietic Stem Cell Self-Renewal and Stress Hematopoiesis via Repression of Cdkn2a.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 1 Downloadable Sample
Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrator regulates transcriptional initiation and pause release following activation.
Sample Metadata Fields
Disease, Cell line, Treatment
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We investigated the genomic occupancy of INTS11, in normal condition and after stimulation of EGF. Total RNAPII was profiled in the presence or absence of INTS11, along with the Super Elongation Complex proteins AFF4 and ELL2. Additionally, we extensively examined the transcriptional response to EGF, before and after depletion of INTS11, using RNA-seq on ribosome-depleted total RNA and Global Run-on sequencing (GRO-seq).
Publication Title
Integrator regulates transcriptional initiation and pause release following activation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To exmaine the PTHLH stimulated genes in Ca9-22 cells, we preformed the Affymetrix Human Genome U133 Plus 2.0 Array with empty vector or PTHLH expression vector. The raw data were normalized by GeneSpring GX software and up-load with raw values.
Publication Title
Parathyroid Hormone-Like Hormone is a Poor Prognosis Marker of Head and Neck Cancer and Promotes Cell Growth via RUNX2 Regulation.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Spinocerebellar ataxia type 3 (SCA3) is one of the polyglutamine (polyQ) diseases, which are caused by a CAG repeat expansion within the coding region of the associated genes.
Publication Title
Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila.
Sample Metadata Fields
Sex, Specimen part
View Samples- Xenopus laevis
- 6 Downloadable Samples
- Affymetrix Xenopus laevis Genome 2.0 Array (xlaevis2)
Description
Exostosin 1 (Ext1) is a glycosyltransferase involved in the biosynthesis of the extracellular matrix Heparan Sulfate Proteoglycan (HSPG). Knockdown of Ext1 caused gastrulation defects and formation of an abnormal body axis. Since ext1 has been implicated as an indirect contributor to multiple signaling pathways in vertebrate development, microarray was used to identify genes expressed in gastrulae that would be affected by a reduction in ext1 expression. Microarray-based comparisons of gene expression in control vs. Ext1 MO embryos showed that Ext1 is involved in regulating genes that are related to metabolic process, development and signaling pathways. Half of the hits from the microarray are uncharacterized genes. Approximately forty-five percent of genes are related to metabolic process and thirty percent of genes are belonged to signaling and developmental process categories. Ten percent of each up-regulated and down-regulated gene set is predicted to function in establishment of localization by GO, which is consistent with EXT1 being involved in the movement of extracellular substances. The transcription factors or signaling protein, Isl1, Pitx2, TBX5A, Wnt5A, Wnt7A, WT1, Pax3, Wnt1, and Xbra were identified as Ext1 regulated genes. This analysis investigating the role of Ext1 during gastrulation and provide the information that EXT1 plays an important role in Xenopus early development. Exostosin 1 (EXT1) is a glycosyltransferase involved in the biosynthesis of the extracellular matrix Heparan Sulfate Proteoglycan (HSPG). Knockdown of EXT1 caused gastrulation defects and formation of an abnormal body axis. Since ext1 has been implicated as an indirect contributor to multiple signaling pathways in vertebrate development, microarray was used to identify genes expressed in gastrulae that would be affected by a reduction in ext1 expression. Microarray-based comparisons of gene expression in control vs. EXT1 MO embryos showed that EXT1 is involved in regulating genes that are related to metabolic process, development and signaling pathways. Half of the hits from the microarray are uncharacterized genes. Approximately forty-five percent of genes are related to metabolic process and thirty percent of genes are belonged to signaling and developmental process categories. Ten percent of each up-regulated and down-regulated gene set is predicted to function in establishment of localization by GO, which is consistent with EXT1 being involved in the movement of extracellular substances. The transcription factors or signaling protein, Isl1, Pitx2, TBX5A, Wnt5A, Wnt7A, WT1, Pax3, Wnt1, and Xbra were identified as EXT1 regulated genes. This analysis investigating the role of EXT1 during gastrulation and provide the information that EXT1 plays an important role in Xenopus early development.
Publication Title
Zygotic expression of Exostosin1 (Ext1) is required for BMP signaling and establishment of dorsal-ventral pattern in Xenopus.
Sample Metadata Fields
Treatment
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Polycomb repressive complex 2-dependent and -independent functions of Jarid2 in transcriptional regulation in Drosophila.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Jarid2 was recently identified as an important component of the mammalian Polycomb Repressive Complex 2 (PRC2), where it has a major effect on PRC2 recruitment in mouse embryonic stem cells. Although Jarid2 is conserved in Drosophila, it has not previously been implicated in Polycomb (Pc) regulation. Therefore, we purified Drosophila Jarid2 and its associated proteins and find that Jarid2 associates with all of the known canonical PRC2 components, demonstrating a conserved physical interaction with PRC2 in flies and mammals. Furthermore, in vivo studies with Jarid2 mutants in flies demonstrate that among several histone modifications tested, only H3K27 methylation, the mark implemented by PRC2, was affected. Genome-wide profiling of Jarid2, Su(z)12 and H3K27me3 occupancy by ChIP-seq indicates that Jarid2 and Su(z)12 have a very similar distribution pattern on chromatin. However, Jarid2 and Su(z)12 occupancy levels at some genes are significantly different with Jarid2 being present at relatively low levels at many Pc response elements (PREs) of certain Homeobox (Hox) genes, providing a rationale for why Jarid2 was never identified in Pc screens. Gene expression analyses show that Jarid2 and E(z) (a canonical PRC2 component) are required not only for transcriptional repression but might also function in active transcription. Identification of Jarid2 as a conserved PRC2 interactor in flies provides an opportunity to begin to probe some of its novel functions in Drosophila development.
Publication Title
Polycomb repressive complex 2-dependent and -independent functions of Jarid2 in transcriptional regulation in Drosophila.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Here we report that Nono instead functions as a chromatin regulator cooperating with Erk to regulate mESC pluripotency. We demonstrate that Nono loss leads to robust self-renewing mESCs with enhanced expression of Nanog and Klf4, epigenome and transcriptome re-patterning to a “ground-like state” with global reduction of H3K27me3 and DNA methylation resembling the Erk inhibitor PD03 treated mESCs and 2i (both GSK and Erk kinase inhibitors)-induced “ground state”. Mechanistically, Nono and Erk co-bind at a subset of development-related, bivalent genes. Ablation of Nono compromises Erk activation and RNA polymerase II C-terminal Domain serine 5 phosphorylation, and while inactivation of Erk evicts Nono from chromatin, revealing reciprocal regulation. Furthermore, Nono loss results in a compromised activation of its target bivalent genes upon differentiation and the differentiation itself. These findings reveal an unanticipated role of Nono in collaborating with Erk signaling to regulate the integrity of bivalent domain and mESC pluripotency. Overall design: mRNA-seq of parental and Nono-KO mES cells
Publication Title
Nono, a Bivalent Domain Factor, Regulates Erk Signaling and Mouse Embryonic Stem Cell Pluripotency.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To examine the transcription targets of RUNX2 in OSCC cells, we preformed the Affymetrix Human Genome U133 Plus 2.0 Array with ectopic RUNX2 or empty vectors in Ca9-22 cells.
Publication Title
Dysregulation of RUNX2/Activin-A Axis upon miR-376c Downregulation Promotes Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples