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Mus musculus
8 Downloadable Samples
Description
Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair.
Publication Title
Parthenogenetic stem cells for tissue-engineered heart repair.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The transcription factor Evi1 is essential for the formation and maintenance of hematopoietic stem cells, and induces clonal dominance with malignant progression upon constitutive activation by chromosomal rearrangements or transgene integration events. To understand the immediate and adaptive response of primary murine hematopoietic cells to the transcriptional upregulation of Evi1, we developed an inducible lentiviral vector system with a robust expression switch. We found that Evi1 delays differentiation and promotes survival in myeloid culture conditions, orchestrating a battery of genes involved in stemness (Aldh1a1, Ly6a [Sca1], Abca1, Epcam, among others). Importantly, Evi1 suppresses Cyclins and Cyclin-dependent kinases (Cdk), while it upregulates Cdk inhibitors, inducing quiescence in various proliferation-inducing cytokine conditions and operating in a strictly dose-dependent manner. Hematopoietic cells with persisting Evi1-induction tend to adopt a relatively low expression level. We thus classify Evi1 as a dormancy-inducing oncogene, likely requiring epigenetic and genetic compensation for cell expansion and malignant progression.
Publication Title
Activation of Evi1 inhibits cell cycle progression and differentiation of hematopoietic progenitor cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
Description
JoMa1 cells are pluripotent precursor cells, derived from the neural crest of mice transgenic for tamoxifen-inducible c-Myc. Following transfection with a cDNA encoding for MYCN, cells become immortlized even in the absence of tamoxifen.
Publication Title
MYCN and ALKF1174L are sufficient to drive neuroblastoma development from neural crest progenitor cells.
Sample Metadata Fields
Specimen part, Cell line
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GSE28736- Mus musculus
- 5 Downloadable Samples
Description
compare wild type and Batf-/- B cells activated for 0 1 or 2 days in vitro.
Publication Title
The transcription factor BATF controls the global regulators of class-switch recombination in both B cells and T cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
Description
The cellular heterogeneity of the brain confounds efforts to elucidate the biological properties of distinct neuronal populations.
Publication Title
A translational profiling approach for the molecular characterization of CNS cell types.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
Description
The cellular heterogeneity of the brain confounds efforts to elucidate the biological properties of distinct neuronal populations.
Publication Title
A translational profiling approach for the molecular characterization of CNS cell types.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The cellular heterogeneity of the brain confounds efforts to elucidate the biological properties of distinct neuronal populations.
Publication Title
A translational profiling approach for the molecular characterization of CNS cell types.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
prenatal stress response, genetic modification
Publication Title
Differential effects of prenatal stress in 5-Htt deficient mice: towards molecular mechanisms of gene × environment interactions.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 23 Downloadable Samples
Description
Studies investigating the causes of autism spectrum disorder (ASD) point to genetic as well as epigenetic mechanisms of the disease. Identification of epigenetic processes that contribute to ASD development and progression is of major importance and may lead to the development of novel therapeutic strategies. Here we identify the bromodomain and extra-terminal domain containing transcriptional regulators (BETs) as epigenetic drivers of an ASD-like disorder in mice. We found that the pharmacological suppression of the BET proteins by a novel, highly selective and brain-permeable inhibitor, I-BET858, leads to selective suppression of neuronal gene expression followed by the development of an autism-like syndrome in mice. Many of the I-BET858 affected genes have been linked to ASD in humans thus suggesting the key role of the BET-controlled gene network in ASD. Our studies also suggest that environmental factors controlling BET proteins or their target genes may contribute to the epigenetic mechanism of ASD.
Publication Title
Autism-like syndrome is induced by pharmacological suppression of BET proteins in young mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Description
The cytosolic protein Sharpin is as a component of the linear ubiquitin chain assembly complex (LUBAC), which regulates NF-B signaling in response to specific ligands. Its inactivating mutation in Cpdm (chronic proliferative dermatitis mutation) mice causes multi-organ inflammation, yet this phenotype is not transferable into wildtype mice by hematopoietic stem cell transfer. Recent evidence demonstrated that Cpdm mice additionally display low bone mass, but the cellular and molecular causes of this phenotype remained to be established. Here we have applied non-decalcified histology together with cellular and dynamic histomorphometry to perform a thorough skeletal phenotyping of Cpdm mice. We show that Cpdm mice display trabecular and cortical osteopenia, solely explained by impaired bone formation, whereas osteoclastogenesis is unaffected. We additionally found that Cpdm mice display a severe disturbance of articular cartilage integrity in the absence of joint inflammation, supporting the concept that Sharpin-deficiency affects mesenchymal cell differentiation. Consistently, Cpdm mesenchymal cells displayed reduced osteogenic capacitiy ex vivo, yet this defect was not associated with impaired NF-B signaling. A molecular comparison of wildtype and Cpdm bone marrow cell populations further revealed that Cpdm mesenchymal cells produce higher levels of Cxcl5 and lower levels of IL1ra. Collectively, our data demonstrate that skeletal defects of Cpdm mice are not caused by chronic inflammation, but that Sharpin is as a critical regulator of mesenchymal cell differentiation and gene expression. They additionally provide an alternative molecular explanation for the inflammatory phenotype of Cpdm mice and the absence of disease transfer by hematopoetic stem cell transplantation.
Publication Title
Sharpin Controls Osteogenic Differentiation of Mesenchymal Bone Marrow Cells.
Sample Metadata Fields
Specimen part
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