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GSE64406
Mus musculus
14 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cell based bone regeneration strategies offer promise for traumatic bone injuries, congenital defects, non-union fractures and other skeletal pathologies. Postnatal bone remodeling and fracture healing provide evidence that an osteochondroprogenitor cell is present in adult life which can differentiate to remodel or repair the fractured bone. However, cell based skeletal repair in the clinic is still in its infancy mostly due to poor characterization of progenitor cells and lack of knowledge about their in vivo behavior. Here we took a combined approach of high throughput screening, flow based cell sorting and in vivo transplantation to identify markers that identify osteochondroprogenitor cells. We show that the presence of tetraspanin CD9 enriches for osteochondroprogenitors within CD105+vemesenchymal cells and these cells readily form bone upon transplantation. In addition we have used Thy1.2 (CD90) and the ectonucleotidase CD73 to identify subsets within the CD9+ve population that lead to endochondral or intramembranous-like bone formation. Utilization of this unique cell surface phenotype to enrich for osteochondroprogenitor cells will allow for further characterization of the molecular mechanisms that regulate their osteogenic properties.
Publication Title
Tetraspanin CD9 and ectonucleotidase CD73 identify an osteochondroprogenitor population with elevated osteogenic properties.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 15 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We generated whole genome expression profiles from a homogeneous population of purified pacemaker neurons (ventral Lateral Neurons, LNvs) from wild type and clock mutant Drosophila. The study identifes a group of genes whose expression is highly enriched in LNvs compared to other neurons; and a second group of genes rhythmically expressed in LNvs in a clock-dependent manner.
Publication Title
A mechanism for circadian control of pacemaker neuron excitability.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study aimed to understand the transcriptional networks regulating endoderm specification from HESC and therefore explored the phenotype of CA1 and CA2 HESC constitutively over-expressing SOX7 or SOX17. Cell lines were created using an inducible construct whereby clonal populations containing transgene integration are selected by Neomycin resistance without expressing of the gene of interest (NoCre controls). Transgene expression is induced via Cre-mediated recombination and selected for puromycin resistance (SOX O/E). The phenotype of the resulting cells suggests that SOX7 expressing HESC represent stable extraembryonic endoderm progenitors, while SOX17 expressing HESC represent early definitive endoderm progenitors. Both in vitro and in vivo SOX7 expressing HESC are restricted to the extraembryonic endoderm lineage, while SOX17 expressing HESC demonstrate mesendodermal specificity. In vitro, SOX17 expressing HESC efficiently produce mature definitive endoderm derivatives.
Publication Title
Establishment of endoderm progenitors by SOX transcription factor expression in human embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Comparison of gene expression signatures in hESC-derived gastrointestinal precursors, enterospheres and primary human tissues to determine lineage and cell type identity.
Publication Title
Functional Enterospheres Derived In Vitro from Human Pluripotent Stem Cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 36 Downloadable Samples
NextSeq500
Description
The Core Binding Factor (CBF) protein RUNX1 is a master regulator of definitive hematopoiesis, crucial for hematopoietic stem cell (HSC) emergence during ontogeny, which also plays vital roles in adult mice, in regulating the correct specification of numerous blood lineages. Akin to the other mammalian Runx genes, Runx1 has two promoters P1 (distal) and P2 (proximal) which generate distinct protein isoforms. The activities and specific relevance of these two promoters in adult hematopoiesis remain to be fully elucidated. Utilizing a dual reporter model, we demonstrate here that the distal P1 promoter is broadly active in adult hematopoietic stem and progenitor cell (HSPC) populations. By contrast, the activity of the proximal P2 promoter is more restricted and its upregulation, in both the immature Lineage- Sca1high cKithigh (LSK) and bipotential Pre-Megakaryocytic/Erythroid Progenitor (PreMegE) populations, coincides with a loss of erythroid specification. Accordingly, the PreMegE population can be prospectively separated into "pro-erythroid" and "pro-megakaryocyte" populations based on Runx1 P2 activity. Comparative gene expression analyses between Runx1 P2+ and P2- populations indicated that the level of CD34 expression could substitute for P2 activity to distinguish these two cell populations in wild type (WT) bone marrow (BM). Prospective isolation of these two populations will provide the opportunity to further investigate and define the molecular mechanisms involved in megakaryocytic/erythroid (Mk/Ery) cell fate decisions. Moreover, comparison of a RUNX1C null (KO) PreMegE to its WT counterpart demonstrated considerably enhanced erythroid specification at the expense of megakaryopoiesis in the absence of P1-specified RUNX1C expression. Overall design: mRNA profiles of wild type (WT), Runx1 P2-hCD4+ (P2+), Runx1 P2-hCD4- (P2-) and RUNX1C knockout (KO) bone marrow Pre-Megakaryocyte/Erythroid (PreMegE) progenitors were generated from young adult (12-16 weeks) mice by deep sequencing, in triplicate, using Illumina NextSeq 500.
Publication Title
RUNX1B Expression Is Highly Heterogeneous and Distinguishes Megakaryocytic and Erythroid Lineage Fate in Adult Mouse Hematopoiesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 700 Downloadable Samples
- NextSeq 500
Description
In recent years, highly detailed characterization of adult bone marrow (BM) myeloid progenitors has been achieved and, as a result, the impact of somatic defects on different hematopoietic lineage fate decisions can be precisely determined. Fetal liver (FL) hematopoietic progenitor cells (HPCs) are poorly characterized in comparison, potentially hindering the study of the impact of genetic alterations on midgestation hematopoiesis. Numerous disorders, for example infant acute leukaemias, have in utero origins and their study would therefore benefit from the ability to isolate highly purified progenitor subsets. We previously demonstrated that a Runx1 distal promoter (P1)-GFP::proximal promoter (P2)-hCD4 dual-reporter mouse (Mus musculus) model can be used to identify adult BM progenitor subsets with distinct lineage preferences. In this study, we undertook the characterization of the expression of Runx1-P1-GFP and P2-hCD4 in FL. Expression of P2-hCD4 in the FL immunophenotypic Megakaryocyte-Erythroid Progenitor (MEP) and Common Myeloid Progenitor (CMP) compartments corresponded to increased granulocytic/monocytic/megakaryocytic and decreased erythroid specification. Moreover, Runx1-P2-hCD4 expression correlated with several endogenous cell surface markers' expression, including CD31 and CD45, providing a new strategy for prospective identification of highly purified fetal myeloid progenitors in transgenic mouse models. We utilized this methodology to compare the impact of the deletion of either total RUNX1 or RUNX1C alone and to determine the fetal HPCs lineages most substantially affected. This new prospective identification of FL progenitors therefore raises the prospect of identifying the underlying gene networks responsible with greater precision than previously possible. Overall design: mRNA profiles of single sorted Runx1 P2-hCD4+ Megakaryocyte Erythroid Progenitors (MEPs), Runx1 P2-hCD4- MEPs, Runx1 P2-hCD4+ Common Myeloid Progenitors (CMPs) and Runx1 P2-hCD4- CMPs from Mouse E14.5 Runx1 P2-GFP::P2-hCD4/+ Fetal Liver Samples
Publication Title
A novel prospective isolation of murine fetal liver progenitors to study in utero hematopoietic defects.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The first lineage decisions during mouse development lead to establishment of embryonic and extraembryonic tissues. The transcription factor Cdx2 plays a central role by repressing pluripotency genes, such as Oct4 and promoting trophoblast fate at the blastocyst stage. Here we show that the transcription factor Gata3 is coexpressed with Cdx2 in the blastocyst and that overexpression of Gata3 in embryonic stem cells is sufficient to induce expression of trophoblast genes. Gata3 expression in the blastocyst does not depend on Cdx2, nor do Gata3 overexpressing cell lines require Cdx2 for expression of a subset of trophoblast genes. In the embryo, expression of Gata3, like Cdx2, depends on Tead4, and expression of both factors becomes restricted to nascent trophoblast by an Oct4-independent mechanism. These observations place Tead4 at the top of a trophoblast hierarchy, with Gata3 and Cdx2 acting downstream to induce expression of common and independent targets in this lineage.
Publication Title
Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To characterized the changes in gene expression during the differentiation of TS cells. TS cells can be derived from two time point during embryogenesis, cell lines tested were from each of these time points.
Publication Title
Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify whether Cdx2 or Gata3 can activate trophoblast specific gene expression when expressed in R1 ES cells. To assess the dependency of Gata3 activity on Cdx2, Gata3 was also expressed in Cdx2-null ES cells.
Publication Title
Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Genomic instability predisposes cells to malignant transformation, however the molecular mechanisms that allow for the propagation of cells with a high-degree of genomic instability remains unclear. Here we report that miR-181a is able to transform fallopian tube secretory epithelial cells- the precursor cell type for the majority of high-grade serous ovarian cancers- through the inhibition of RB1 and simultaneously drives a cell protective inhibition of the stimulator-of-interferon-genes (STING) in order to maintain a microenvironment conducive to the propagation of cells with a high-degree of genomic instability. We found that miR-181a inhibition of RB1 leads to profound nuclear defects, genomic instability, and nuclear rupture resulting in a persistence of genomic material in the cytoplasm. While normally, this persistence of genomic material in the cytoplasm induces interferon response through STING to drive cell death, miR-181a directly downregulates STING and prevents apoptosis. The most common mechanism by which oncogenic miRNAs promote tumorigenesis is through the direct inhibition of tumor suppressor genes, however our studies highlight a new mechanism of oncomiR transformation through the combination of tumor suppressor gene inhibition and abrogation of immune surveillance that initiates and propagates tumor cell survival. Importantly, we found that miR-181a induction in ovarian patient tumors is tightly associated with decreased IFNg response and downregulation of lymphocyte infiltration amd leukocyte fraction. To date, DNA oncoviruses are the only known inhibitors of STING that allow for cellular transformation thus, our findings are the first to identify a genetic factor, miR-181a, that can downregulate STING expression, suppress activation of the immunosurveillance machinery, and impair signaling in cancer cells creating a survival advantage. Our studies support the notion that the induction of STING-mediated signaling in cancer cells could lead directly to cancer cell death however these effects are abrogated by miR-181a. Given the recent interest in the development of STING agonists as a strategy to harness the immune system to treat cancer, this study introduces novel patient selective biomarker as well as potent therapeutic target for development of the most effective combination treatments.
Publication Title
miR-181a initiates and perpetuates oncogenic transformation through the regulation of innate immune signaling.
Sample Metadata Fields
No sample metadata fields
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