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accession-icon GSE46534
Development of MLL-rearranged leukemia is dependent on a transcriptional program orchestradt by C/EBP
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Translocations involving the MLL genes are frequently found in Acute Myeloid Leukemia (AML) and are associated with poor prognosis. The MLL fusion proteins act as aberrant transcription factor activating a transcriptional program that transforms the cells, potentially through collaboration with other transcription factors. To investigate this we searched gene expression profiles from patients with MLL-rearranged AML compared with normal hematopoietic progenitor cells for transcriptional regulators and found targets of C/EBP to be up-regulated in the AML samples, suggesting that C/EBP might collaborate with MLL fusion proteins in the initial transformation process. We could show that transformation by MLL fusion proteins is dependent on C/EBP activity both in early progenitors as well as in GMPs. In contrast, C/EBP was found to be indispensable in an already established leukemia. These results suggest that C/EBP play an important role in the early transforming event of leukemogenesis.

Publication Title

Initiation of MLL-rearranged AML is dependent on C/EBPα.

Sample Metadata Fields

Specimen part

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accession-icon GSE42498
Deletion of Cebpa from HSCs
  • organism-icon Mus musculus
  • sample-icon 7 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

In this study, we use a conditional mouse model for Cebpa to investigate the significance of C/EBP in HSCs. The frequency of HSCs is unaltered following deletion of C/EBP, however, upon serial transplantations of either full BM or purified HSCs, the stem cells and stem cell activity is lost. This is not due to increased proliferation, but rather caused by a shift from quiescence to apoptosis with a resultant exhaustion of the stem cell pool. We identify direct C/EBP target genes by combining genome-wide C/EBP ChIP-seq analysis in stem and progenitor cells with gene expression data from HSC with and without C/EBP. Furthermore, we explore the impact of C/EBP on active and repressive histone modifications by doing functional genome-wide ChIP-seq analysis of H3K4Me3 and H3K27Me3 in stem and progenitor cells with and without C/EBP.

Publication Title

C/EBPα is required for long-term self-renewal and lineage priming of hematopoietic stem cells and for the maintenance of epigenetic configurations in multipotent progenitors.

Sample Metadata Fields

Sex, Specimen part

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accession-icon SRP063520
Transcriptional heterogeneity and lineage commitment in myeloid progenitors [single cell RNA-seq]
  • organism-icon Mus musculus
  • sample-icon 54 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

Within the bone marrow, hematopoietic stem cells differentiate and give rise to diverse blood cell types and functions. Currently, hematopoietic progenitors are defined using surface markers combined with functional assays that are not directly linked with the in vivo potential or gene regulatory mechanisms. Here we comprehensively identify myeloid progenitor subpopulations by transcriptional sorting of single cells from the bone marrow. We describe multiple progenitor subgroups showing unexpected transcriptional priming towards seven differentiation fates, but no progenitors with a mixed state. Transcriptional differentiation is correlated with combinations of known and previously undefined transcription factors, suggesting the process is tightly regulated. Histone maps and knockout assays are consistent with the transcriptional states while traditional transplantation experiments are only partially overlapping myeloid transcriptional priming. Our analyses uncover the function of the underlying regulatory mechanisms for several sub groups and establishes a general framework for dissecting hematopoiesis. Overall design: Bone marrow Lin- cKit+ Sca1- myeloid progenitors mRNA profiles from single cells were generated by deep sequencing of thousands of single cells, sequenced in several batches in an Illumina NextSeq Please note that [1] raw data files were processed as single-ended file since second read (mate) files contain only cell/molecule barcodes and therefore, not provided. This information was appended to the fastq entry header [2] The ''experimental_design.txt'' file explains the correspondence of each single cell (WXXXX) in the ''umitab.txt'' to a sample (ABXXXX).

Publication Title

Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors.

Sample Metadata Fields

Specimen part, Cell line, Treatment, Subject

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accession-icon GSE41856
Cell growth in aggregates determines gene expression, proliferation, survival and chemoresistance of Follicular Lymphoma
  • organism-icon Homo sapiens
  • sample-icon 14 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Cell growth in aggregates determines gene expression, proliferation, survival, chemoresistance, and sensitivity to immune effectors in follicular lymphoma.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE41855
Expression data from quiescent cells and cycling cells isolated from Multicellular aggregates of lymphoma cells (MALC)
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Follicular Lymphomas are blood tumors growing as spheres in patients. Before this study, there was no experimental model mimicking the 3D organization of these in vivo tumors. We develop such a model, called MALC, and observed a progressive enrichment in quiescent cells in these with time of culture; these cells were sorted, as their cycling counterparts, and their transcriptomes were compared. We used microarrays to detail the differential global gene expression profile between quiescent and cycling cells isolated from MALC.

Publication Title

Cell growth in aggregates determines gene expression, proliferation, survival, chemoresistance, and sensitivity to immune effectors in follicular lymphoma.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE41851
Expression data from follicular lymphoma cells cultured either in suspension either as Multicellular aggregates of lymphoma cells (MALC)
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Follicular Lymphomas are blood tumors growing as spheres in patients. Before this study, there was no experimental model mimicking the 3D organization of these in vivo tumors. We develop such a model, called MALC, and performed a pan-genomic comparative analysis between MALC and classical suspension cultures. We used microarrays to detail the global gene expression profile induced by aggregated growth of lymphoma cells.

Publication Title

Cell growth in aggregates determines gene expression, proliferation, survival, chemoresistance, and sensitivity to immune effectors in follicular lymphoma.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE84072
Expression data from CD8+TIM-3+ and CD8+TIM-3- T cells sorted from follicular lymphoma lymph nodes
  • organism-icon Homo sapiens
  • sample-icon 3 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 2.0 ST Array (hugene20st)

Description

Exhaustion markers are expressed by T lymphocytes in Follicular Lymphoma (FL). Through these, TIM-3 has been recently identified as a poor pronostic factor when expressed by FL CD4+ T cells.

Publication Title

Impaired functional responses in follicular lymphoma CD8<sup>+</sup>TIM-3<sup>+</sup> T lymphocytes following TCR engagement.

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE31280
Transcript level in F9 teratocarcinoma WT and RARalpha knockout in presence and absence of all-trans retinoic acid
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Retinoic acid receptors (RARs) , and are key regulators of embryonic development. Hematopoietic differentiation is regulated by RAR, and several types of leukemia show aberrant RAR activity. We demonstrate that RAR plays an important role in cellular memory and imprinting by regulating the CpG methylation status of specific promoter regions.

Publication Title

Epigenetic regulation by RARα maintains ligand-independent transcriptional activity.

Sample Metadata Fields

Cell line, Treatment

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accession-icon GSE64919
Genes regulated in EML1 cells expressing the TEL-AML1 oncogene after 5 and 7 days of treatment with IL7 and FLT3 ligand.
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.1 ST Array (mogene11st)

Description

The t(12;21) translocation is the most common genetic rearrangement in childhood acute lymphoblastic leukemia (ALL) and gives rise to the TEL-AML1 fusion gene, which functions as a transcription factor.

Publication Title

The TEL-AML1 fusion protein of acute lymphoblastic leukemia modulates IRF3 activity during early B-cell differentiation.

Sample Metadata Fields

Cell line, Treatment

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accession-icon GSE29305
NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming
  • organism-icon Mus musculus, Homo sapiens
  • sample-icon 19 Downloadable Samples
  • Technology Badge IconIllumina MouseRef-8 v2.0 expression beadchip

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming.

Sample Metadata Fields

Sex, Age, Specimen part, Cell line

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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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