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accession-icon SRP200493
Mapping distinct bone marrow niche populations and their differentiation paths
  • organism-icon Mus musculus
  • sample-icon 5 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

The bone marrow microenvironment is composed of heterogeneous cell populations of non-hematopoietic cells with complex phenotypes and undefined trajectories of maturation. Among them, mesenchymal cells maintain the production of stromal, bone, fat and cartilage cells. Resolving these unique cellular subsets within the bone marrow remains challenging. Here, we used single-cell RNA-sequencing of non-hematopoietic bone marrow cells to define specific subpopulations. Furthermore, by combining computational prediction of the cell state hierarchy with known expression of key transcription factors, we mapped differentiation paths to the osteocyte, chondrocyte, and adipocyte lineages. Finally, we validated our findings using lineage-specific reporter strains and targeted knockdowns. Our analysis reveals differentiation hierarchies for maturing stromal cells, determines key transcription factors along these trajectories, and provides an understanding of the complexity of the bone marrow microenvironment. Overall design: Single-cell mRNA sequencing of stromal cells from mouse bone marrow. Sample Stroma1 represents 948 final filtered single cells. Sample Stroma2 represents 1899 final filtered single cells.

Publication Title

Mapping Distinct Bone Marrow Niche Populations and Their Differentiation Paths.

Sample Metadata Fields

Specimen part, Cell line, Subject

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accession-icon GSE43811
CD109 plays a role in osteoclastogenesis.
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

The primary aim of this project was to identify novel factors, in particular the cell-surface protein CD109, which regulate osteoclastogenesis. Microarray analysis was performed comparing two pre-osteoclast cell lines generated from the RAW 264.7 osteoclast cell line: one that has the capacity to fuse forming large multinucleated cells and one that does not fuse. It was found that CD109 was up-regulated by > 17-fold in the osteoclast forming cell line when compared to the cell line that does not fuse.

Publication Title

CD109 plays a role in osteoclastogenesis.

Sample Metadata Fields

Specimen part, Cell line

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accession-icon GSE38222
Stau2 RIP-Chip in Mouse E13-14 Cortex
  • organism-icon Mus musculus
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

The double-stranded RNA binding protein Staufen2 (Stau2) is asymmetrically localized and segregated during asymmetric cell divisions in the developing mouse cortex and promotes intermediate progenitor cell fate.

Publication Title

Asymmetric segregation of the double-stranded RNA binding protein Staufen2 during mammalian neural stem cell divisions promotes lineage progression.

Sample Metadata Fields

Specimen part

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accession-icon GSE13110
MYB silencing in CD34+ progenitor cells
  • organism-icon Homo sapiens
  • sample-icon 3 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A Array (hgu133a)

Description

The c-Myb transcription factor is highly expressed in immature hematopoietic cells and down-regulated during differentiation. To define the role of c-Myb in human hematopoietic lineage commitment, we studied the effects of its silencing during the commitment of human CD34+ Hematopoietic stem/progenitor cells. In CD34+ cells c-Myb silencing determined a cell cycle arrest in G0/G1 phase which strongly decreased the clonogenic efficiency, togheter with a reduction of erythroid colonies coupled with an increase of the macrophage and megakaryocyte ones. Moreover, morphological and flow cytometry data supported the preferential macrophage and megakaryocyte differentiation of c-Myb-silenced CD34+ cells. Taken together our data indicate that c-Myb is essential for the commitment along the erythroid and granulocyte lineages but not for the macrophage and megakaryocyte differentiation. Gene expression profiling of c-Myb-silenced CD34+ cells identified some potential c-Myb targets which can account for these effects, to study by Chromatin Immunoprecipitation and Luciferase Reporter Assay.

Publication Title

c-myb supports erythropoiesis through the transactivation of KLF1 and LMO2 expression.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE21943
MYB silencing in CD14-myeloblasts
  • organism-icon Homo sapiens
  • sample-icon 3 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A Array (hgu133a)

Description

The c-Myb transcription factor is highly expressed in immature hematopoietic cells and down-regulated during differentiation. To define the role of c-Myb during the terminal differentiation of hematopoietic precursors, we studied the effects of its silencing in human primary CD14-myeloblasts, which maintain a granulo-monocyte differentiation bipotentiality. c-Myb-silenced myeloblasts were blocked in the G1 phase of the cell cycle at 24 hours post-nucleofection and subsequently were forced towards macrophage differentiation, as demonstrated by immunophenotypic and morphological analysis. Indeed, c-Myb-silenced CD14- cells differentiate to macrophage even after the treatment with ATRA 10-6 M, demonstrating that the c-Myb knockdown strongly impairs the ability of myeloblasts to differentiate to granulocytes. Gene expression profiling of c-Myb-silenced CD14- cells identified some potential c-Myb targets that can account for these effects.

Publication Title

c-myb supports erythropoiesis through the transactivation of KLF1 and LMO2 expression.

Sample Metadata Fields

Specimen part, Time

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accession-icon E-MEXP-2072
Transcription profiling of mouse leukemia initiation cells of SALL4B transgenic strains and their control counterparts
  • organism-icon Mus musculus
  • sample-icon 20 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)

Description

To compare the gene expression profiles of leukemia initiation cells of SALL4B transgenic mice and their control counterparts.

Publication Title

A SALL4/MLL/HOXA9 pathway in murine and human myeloid leukemogenesis.

Sample Metadata Fields

Specimen part, Disease

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accession-icon GSE42234
C/EBPa controls acquisition and maintenance of adult hematopoietic stem cell quiescence
  • organism-icon Mus musculus
  • sample-icon 17 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

In blood, the transcription factor C/EBPa is essential for myeloid differentiation and has been implicated in regulating self-renewal of fetal liver hematopoietic stem cells (HSCs). However, its function in adult HSCs is unknown. Here, using an inducible knockout model, we found that C/EBPa deficient adult HSCs underwent a pronounced expansion with enhanced proliferation, characteristics resembling fetal liver HSCs. Consistently, transcription profiling of C/EBPa deficient HSCs revealed a gene expression program similar to fetal liver HSCs. Moreover we observed that age-specific C/EBPa expression correlated with its inhibitory effect on the HSC cell cycle. Mechanistically, we identified N-Myc as a C/EBPa downstream target. C/EBPa upregulation during HSC transition from an active fetal state to a quiescent adult state was accompanied by down-regulation of N-Myc, and loss of C/EBPa resulted in de-repression of NMyc. Our data establish that C/EBPa acts as a molecular switch between fetal and adult states of HSC in part via transcriptional repression of the proto-oncogene N-Myc.

Publication Title

C/EBPa controls acquisition and maintenance of adult haematopoietic stem cell quiescence.

Sample Metadata Fields

Specimen part

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accession-icon GSE31040
Gene expression analysis of human lymphoblastoid cell lines
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Human lymphoblastoid cell lines (EBV-immortalised B cells, LcL) obtained from subjects of different age (young 28-40 years, centenarians >95 years) were analysed for gene expression at basal culture conditions and after 48 hours of serum starvation. Lymphoid B cells from centenarians were more resistant to apoptosis induction and displayed a more developed lysosomal compartment, the most critical component of phagic machinery. In addition, cells from centenarians were capable of engulfing and digesting other cells, i.e. their siblings (even entire cells). This behavior was improved by nutrient deprivation, but strikingly, it was unaffected by the autophagy-modulating drugs rapamycin, an autophagy inducer, and 3-methyladenine, an autophagy inhibitor.

Publication Title

Survival features of EBV-stabilized cells from centenarians: morpho-functional and transcriptomic analyses.

Sample Metadata Fields

Sex, Age, Specimen part, Subject

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accession-icon SRP153550
RNA-seq analysis comparing gene expression in Drosophila sea mutants and controls
  • organism-icon Drosophila melanogaster
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

The goal of this study was to determine how decreased mitochondrial citrate export influences gene expression in Drosophila larvae. RNA was isolated from Drosopohila sea mutants, which exhibiti decreased mitochondrial citrate transport activity, and a genetically-matched control strain during mid-L3 development. Overall design: Larvae were collected as described in Li, H., Tennessen, J. M. Preparation of Drosophila Larval Samples for Gas Chromatography-Mass Spectrometry (GC-MS)-based Metabolomics. J. Vis. Exp. (136), e57847, doi:10.3791/57847 (2018). RNA was purified from staged mid-L3 larvae using a RNeasy Mini Kit (Qiagen). Sequencing was performed using an Illumina NextSeq500 platform with 75 bp sequencing module generating 41 bp paired-end reads. After the sequencing run, demultiplexing was performed with bcl2fastq v2.20.0.422.

Publication Title

A <i>Drosophila</i> model of combined D-2- and L-2-hydroxyglutaric aciduria reveals a mechanism linking mitochondrial citrate export with oncometabolite accumulation.

Sample Metadata Fields

Subject

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accession-icon GSE43998
C/EBPa gene signature
  • organism-icon Homo sapiens
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

We defined the C/EBPa signature characterized by a set of genes which are upregulated upon C/EBPa activation. In order to identify the C/EBPa signature, we performed microarray gene expression analysis of K562 cells stably expressing p42-C/EBPa-ER after activating the C/EBPa construct to translocate to the nucleus for 6 hours with beta-estradiol.

Publication Title

The gene signature in CCAAT-enhancer-binding protein α dysfunctional acute myeloid leukemia predicts responsiveness to histone deacetylase inhibitors.

Sample Metadata Fields

Cell line, Treatment

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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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