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accession-icon GSE57004
Cpeb4-mediated Translational Regulatory Circuitry Controls Terminal Erythroid Differentiation
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

Description

Erythropoiesis is essential to mammals and is regulated at multiple steps by both extracellular and intracellular factors. Many transcriptional regulatory networks in erythroid differentiation have been well characterized. However, our understanding of post-transcriptional regulatory circuitries in this developmental process is still limited. Using genomic approaches, we identified a sequence-specific RNA-binding protein, Cpeb4, which is dramatically induced in terminal erythroid differentiation (TED) by two erythroid important transcription factors, Gata1/Tal1. Cpeb4 belongs to the cytoplasmic polyadenylation element binding (CPEB) protein family that regulates translation of target mRNAs in early embryonic development, neuronal synapse, and cancer. Using primary mouse fetal liver erythroblasts, we found that Cpeb4 is required for terminal erythropoiesis by repressing the translation of a set of mRNAs highly expressed in progenitor cells. This translational repression occurs by the interaction with a general translational initiation factor, eIF3. Interestingly, Cpeb4 also binds its own mRNA and represses its translation, thus forming a negative regulatory circuitry to limit Cpeb4 protein level. This mechanism ensures that the translation repressor, Cpeb4, does not interfere with the translation of other mRNAs in differentiating erythroblasts. Our study characterized a translational regulatorycircuitry that controls TED and revealed that Cpeb4 is required for somatic cell differentiation.

Publication Title

Cpeb4-mediated translational regulatory circuitry controls terminal erythroid differentiation.

Alternate Accession IDs

E-GEOD-57004

Sample Metadata Fields

Specimen part

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accession-icon GSE20391
Comprehensive expression profiling across primary fetal liver terminal erythroid differentiation
  • organism-icon Mus musculus
  • sample-icon 11 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Primary murine fetal liver cells were freshly isolated from day e14.5 livers and then sorted for successive differentiation stages by Ter119 and CD71 surface expression (ranging from double-negative CFU-Es to Ter-119 positive enucleated erythrocytes) [Zhang, et al. Blood. 2003 Dec 1; 102(12):3938-46]. RNA isolated from each freshly isolated, stage-sorted population was reverse-transcribed, labelled, and then hybridized onto 3' oligo Affymetrix arrays. Important erythroid specific genes as well as the proteins that regulate them were elucidated through this profiling based on coexpression and differential expression patterns as well as by extracting specific GO categories of genes (such as DNA-binding proteins).

Publication Title

Homeodomain-interacting protein kinase 2 plays an important role in normal terminal erythroid differentiation.

Alternate Accession IDs

E-GEOD-20391

Sample Metadata Fields

Specimen part

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accession-icon SRP012062
RNA-sequencing analysis of NB4 cells overexpressing miR-125b
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer

Description

To better understand the mechanisms of blockage of myeloid differentiation and apoptosis and induction of proliferation by miR-125b, we proceeded to identify miR-125b target genes involved in these pathways. We analyzed the total cellular gene expression pattern by RNA-sequencing of the parental NB4 myeloid cell line and that transiently transfected with miR-125b. We generated four cDNA libraries corresponding to duplicates of miR-125b and control cells. Overall design: Compare the gene expression levels in miR control transfected cells with that in miR-125b transfected NB4 cells. 

Publication Title

MicroRNA-125b transforms myeloid cell lines by repressing multiple mRNA.

Alternate Accession IDs

GSE37061

Sample Metadata Fields

Specimen part, Cell line, Subject

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accession-icon SRP012041
RNA-sequencing analysis of 32Dclone3 cells overexpressing miR-125b
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer

Description

To better understand the mechanisms of blockage of myeloid differentiation and apoptosis and induction of proliferation by miR-125b, we preceded to identify miR-125b target genes involved in these pathways. We analyzed the total cellular gene expression pattern by RNA-sequencing of the parental 32Dclone3 myeloid cell line and that ectopically expressing miR-125b. We generated four cDNA libraries corresponding to duplicates of miR-125b and control cells. Overall design: Compare the gene expression level in vector transduced 32Dclone3 cells with that in miR-125b transduced 32Dclone3 cells. 

Publication Title

MicroRNA-125b transforms myeloid cell lines by repressing multiple mRNA.

Alternate Accession IDs

GSE37018

Sample Metadata Fields

Specimen part, Cell line, Subject

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accession-icon SRP004639
RNA-Seq analysis of microRNA expression profiles in mouse primary CFU-E late erythroid progenitors and Ter119+ mature erythroblasts
  • organism-icon Mus musculus
  • sample-icon 2 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer II

Description

Using RNA-seq technology, we quantitatively determined the expression profile of microRNAs during mouse terminal erythroid differentiation. CFU-E erythroid progenitors were isolated from E14.5 fetal liver as the Ter119, B220, Mac-1, CD3 and Gr-1 negative, C-Kit positive and 20% high CD71 population. Mature Ter119+ erythroblasts were isolated from E14.5 fetal liver as C-Kit negative and Ter119 positive population. Consistent with nuclear condensation and global gene expression shut down during terminal erythroid differentiation, we found that the majority of microRNAs are downregulated in more mature Ter119+ erythroblasts compared with CFU-E erythroid progenitors. Overall design: Examination of microRNA expression profiles in 2 cell types

Publication Title

miR-191 regulates mouse erythroblast enucleation by down-regulating Riok3 and Mxi1.

Alternate Accession IDs

GSE25602

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP050511
Synergism between PPARa and glucocorticoid receptor signaling promotes self-renewal of BFU-E erythroid progenitors and increases red cell production [RNA-seq]
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Analyses of gene expression by RNA-Seq in mouse E14.5 fetal liver burst-forming unit erythroid (BFU-E) cells untreated or treated by dexamethasone (DEX) with or without PPARa agonist GW7647. Overall design: RNA-Seq was performed on enriched populations of mouse BFU-E isolated from E14.5 fetal liver, as well as BFU-E enriched cells treated with Dex ± GW7647.

Publication Title

PPAR-α and glucocorticoid receptor synergize to promote erythroid progenitor self-renewal.

Alternate Accession IDs

GSE63836

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP049324
RNA-seq expression profiles during terminal erythropoiesis
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer

Description

It is unclear how epigenetic changes regulate the induction of erythroid-specific genes during terminal erythropoiesis. Here we use global mRNA sequencing (mRNA-seq) and chromatin immunoprecipitation coupled to high-throughput sequencing (CHIP-seq) to investigate the changes that occur in mRNA levels, RNA Polymerase II (Pol II) occupancy and multiple post-translational histone modifications when erythroid progenitors differentiate into late erythroblasts. Among genes induced during this developmental transition, there was an increase in the occupancy of Pol II, the activation marks H3K4me2, H3K4me3, H3K9Ac and H4K16Ac, and the elongation methylation mark H3K79me2. In contrast, genes that were repressed during differentiation showed relative decreases in H3K79me2 levels yet had levels of Pol II binding and active histone marks similar to those in erythroid progenitors. We also found that relative changes in histone modification levels-in particular, H3K79me2 and H4K16ac-were most predictive of gene expression patterns. Our results suggest that in terminal erythropoiesis both promoter and elongation-associated marks contribute to the induction of erythroid genes, while gene repression is marked by changes in histone modifications mediating Pol II elongation. Our data maps the epigenetic landscape of terminal erythropoiesis and suggests that control of transcription elongation regulates gene expression during terminal erythroid differentiation. Overall design: Mouse fetal liver cells are double-labeled for erythroid-specific TER119 and non erythroid-specific transferrin receptor (CD71) and then sorted by flow-cytometry. E14.5 fetal livers contain at least five distinct populations of cells (R1 through R5); as they progressively differentiate they gain TER119 and then gain and subsequently lose CD71. CFU-E cells and proerythroblasts make up the R1 population; R2 consists of proerythroblasts and early basophilic erythroblasts; R3 includes early and late basophilic erythroblasts; R4 is mostly polychromatophilic and orthochromatophilic erythroblasts; and R5 is comprised of late orthochromatophilic erythroblasts and reticulocytes. We have sorted for R2-R5 cells for RNA-seq experiment.

Publication Title

Gene induction and repression during terminal erythropoiesis are mediated by distinct epigenetic changes.

Alternate Accession IDs

GSE32110

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP154186
Single cell RNA sequencing of primary-isolated erythroid progenitors [Days 1-3]
  • organism-icon Mus musculus
  • sample-icon 576 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

single cell RNA sequencing of freshly isolated mouse BFU-E (burst forming unit-erythroid ) cells cultured for 1, 2, or 3 days with and without 100nM dexamethasone Overall design: six 96 well plates

Publication Title

Rate of Progression through a Continuum of Transit-Amplifying Progenitor Cell States Regulates Blood Cell Production.

Alternate Accession IDs

GSE117231

Sample Metadata Fields

Specimen part, Cell line, Treatment, Subject

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accession-icon SRP154147
Single cell RNA sequencing of primary-isolated erythroid progenitors [BFUE, CFUE, intermediates]
  • organism-icon Mus musculus
  • sample-icon 96 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Single cell RNA sequencing of freshly isolated mouse burst forming unit-erythroid (BFU-E) , colony forming unit-erythroid (CFU-E), and intermediate stages of erythroid development cells. Overall design: One 96 well plate with 24 BFU-E, 24 CFU-E, 24 cells with 25-35% expression of CD71/CD24, and 24 cells with 50-60% expression of CD71/CD24.

Publication Title

Rate of Progression through a Continuum of Transit-Amplifying Progenitor Cell States Regulates Blood Cell Production.

Alternate Accession IDs

GSE117228

Sample Metadata Fields

Specimen part, Cell line, Subject

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accession-icon SRP154149
Single cell RNA sequencing of primary-isolated erythroid progenitors [daughter cells]
  • organism-icon Mus musculus
  • sample-icon 52 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Single cell mouse BFU-E (burst forming unit-erythroid ) were FACS-deposited into individual wells of a 96-well plate containing PCM either with or without 100 nM dexamethasone. After 16hrs cells from wells that contained a single pair of daughter cells were separated and each individual daughter cell transcriptome was obtained by single cell RNA-seq. Overall design: 13 daughter cells pairs untreated and 13 pairs treated with 100 nM dexamethasone.

Publication Title

Rate of Progression through a Continuum of Transit-Amplifying Progenitor Cell States Regulates Blood Cell Production.

Alternate Accession IDs

GSE117232

Sample Metadata Fields

Specimen part, Cell line, Treatment, Subject

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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