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GSE68834
Mus musculus
13 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hematopoietic stem cell (HSC) are regulated by their niche, which limits activation of HSCs, to ensure their maintenance and self-renewal.
Publication Title
Stroma-Derived Connective Tissue Growth Factor Maintains Cell Cycle Progression and Repopulation Activity of Hematopoietic Stem Cells In Vitro.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 32 Downloadable Samples
Illumina HiSeq 1500
Description
Mesenchymal stromal cells (MSC) are crucial components of the bone marrow (BM) microenvironment essential for regulating self-renewal, survival and differentiation of hematopoietic stem/progenitor cells (HSPC) in the stem cell niche. MSC are functionally and phenotypically altered in myelodysplastic syndromes (MDS), contributing to disease progression. MDS MSC do not harbor recurrent genetic alterations but have been shown to exhibit an altered methylome compared to MSC from healthy controls. We examined growth, differentiation and HSPC-supporting capacity of ex vivo expanded MSC from MDS patients in comparison to age-matched healthy controls after direct treatment in vitro with the hypomethylating agent azacitidine (AZA). We show that AZA exerts a direct effect on MSC by modulating their differentiation potential. Osteogenesis was significantly boosted in healthy MSC while adipogenesis was inhibited in both healthy and MDS MSC. In co-culture experiments, both AZA treated MDS MSC and healthy MSC exhibited enhanced support of non-clonal HSPC which was associated with increased cell cycle induction. Conversely, clonal MDS HSPC were inhibited by contact with AZA treated MSC. RNA-sequencing analyses of stromal cells revealed changes in pathways essential for HSPC support as well as in immune regulatory pathways. In sum, our data demonstrate that AZA treatment of stromal cells leads to upregulation of HSPC-supportive genes and cell cycle induction in co-cultured healthy HSPC, resulting in a proliferative advantage over clonal HSPC. Thus, restoration of functional hematopoiesis by AZA may be driven by activated stromal support factors in MSC providing cell cycle cues to healthy HSPC. Overall design: RNA sequencing was performed on a mesenchymal stromal cell line (EL08-1D2), either untreated or treated with Azacitidine [(-)AZA vs. (+)AZA].
Publication Title
Direct modulation of the bone marrow mesenchymal stromal cell compartment by azacitidine enhances healthy hematopoiesis.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Thymocyte selection-associated high mobility group box protein family member 2 (TOX2) is a transcription factor belonging to the TOX family that shares a highly conserved high mobility group DNA binding domain with the other TOX members. While TOX1 has been shown to be an essential regulator of T-cell and natural killer (NK) cell differentiation in mice, little is known about the roles of the other TOX family members in lymphocyte development, particularly in humans. In this study, we found that TOX2 was preferentially expressed in mature human NK cells and was upregulated during in vitro differentiation of NK cells from human umbilical cord blood (UCB)derived CD34+ cells. Gene silencing of TOX2 intrinsically hindered the transition between early developmental stages of NK cells, while overexpression of TOX2 enhanced the development of mature NK cells from UCB CD34+ cells. We subsequently found that TOX2 was independent of ETS-1 but could directly upregulate the transcription of TBX21 (encoding T-BET). Overexpression of T-BET rescued the TOX2 knockdown phenotypes. Given the essential function of T-BET in NK cell differentiation, TOX2 therefore plays a crucial role in controlling normal NK cell development by acting upstream of TBX21 transcriptional regulation.
Publication Title
TOX2 regulates human natural killer cell development by controlling T-BET expression.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Hematopoietic stem cells (HSCs) are identified by their ability to sustain prolonged blood cell production in vivo, although recent evidence suggests that durable self-renewal (DSR) is shared by HSC subtypes with distinct self-perpetuating differentiation programs. Net expansions of DSR-HSCs occur in vivo, but molecularly defined conditions that support similar responses in vitro are lacking. We hypothesized that this might require a combination of factors that differentially promote HSC viability, proliferation and self-renewal. We now demonstrate that HSC survival and maintenance of DSR potential is variably supported by different Steel factor (SF)-containing cocktails with similar HSC-mitogenic activities. In addition, stromal cells produce other factors, including nerve growth factor and collagen 1, that can antagonize the apoptosis of initially quiescent adult HSCs and, in combination with SF and interleukin-11, produce >15-fold net expansions of DSR-HSCs ex vivo within 7 days. These findings suggest a new molecular basis for HSC control and expansion.
Publication Title
Distinct stromal cell factor combinations can separately control hematopoietic stem cell survival, proliferation, and self-renewal.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hematopoiesis occurs in a microenviroenment in which stromal cells are prominent. Stromal cells have been shown to maintain stem cell behaviour of hematopoietic stem cells. We derived several different stromal cell lines from midgestation embryos which will, or will not maintain hemetopoietic stem cells in cultures.
Publication Title
Efficient hematopoietic differentiation of human embryonic stem cells on stromal cells derived from hematopoietic niches.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
JAK/STAT3 signalling is sufficient and dominant over antagonistic cues for the establishment of naive pluripotency.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This microarray was performed to gain insight in the effect of GY118F stimulation in EpiSCs. This array is part of the following paper to be published in Nature Communications: JAK/STAT3 signalling is sufficient and dominant over antagonistic cues for the establishment of nave pluripotency by Anouk L. van Oosten, Yael Costa, Austin Smith & Jos C.R. Silva
Publication Title
JAK/STAT3 signalling is sufficient and dominant over antagonistic cues for the establishment of naive pluripotency.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This microarray was performed to gain insight in the downstream targets of GY118F in iPS cells. This array is part of the following paper to be published in Nature Communications: JAK/STAT3 signalling is sufficient and dominant over antagonistic cues for the establishment of nave pluripotency by Anouk L. van Oosten, Yael Costa, Austin Smith & Jos C.R. Silva
Publication Title
JAK/STAT3 signalling is sufficient and dominant over antagonistic cues for the establishment of naive pluripotency.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Protein kinase c-β-dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. Here we describe a novel survival signaling pathway activated in stromal cells by contact to B-cells from chronic lymphocytic leukemia (CLL) patients. The expression of PKC-II and the subsequent activation of NF-B in bone marrow stromal cells is a prerequisite to support the survival of malignant B-cells. PKC- knockout mice are insusceptible to CLL-transplantations, underscoring the in vivo significance of the PKC-II- NF-B signaling pathway in the tumor microenvironment. Upregulated stromal PKC-II in biopsies from CLL, breast- and pancreatic- cancer patients suggest that this pathway may commonly be activated in a variety of malignancies.
Publication Title
Protein kinase c-β-dependent activation of NF-κB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia B cells in vivo.
Sample Metadata Fields
Specimen part
View Samples