We have recently shown a remarkable regenerative capacity of the prenatal heart using a genetic model of mosaic mitochondrial dysfunction in mice. This model is based on inactivation of the X-linked gene encoding holocytochrome c synthase (Hccs) specifically in the developing heart. Loss of HCCS activity results in respiratory chain dysfunction, disturbed cardiomyocyte differentiation and reduced cell cycle activity. The Hccs gene is subjected to X chromosome inactivation, such that in females heterozygous for the heart conditional Hccs knockout approximately 50% of cardiac cells keep the defective X chromosome active and develop mitochondrial dysfunction while the other 50% remain healthy. During heart development, however, the contribution of HCCS deficient cells to the cardiac tissue decreases from 50% at midgestation to 10% at birth. This regeneration of the prenatal heart is mediated by increased proliferation of the healthy cardiac cell population, which compensate for the defective cells and allow the formation of a fully functional heart at birth. Here we performed microarray expression ananlyses on 13.5 dpc control and heterozygous Hccs knockout hearts to identify molecular mechanisms that drive embryonic heart regeneration.
Embryonic cardiomyocytes can orchestrate various cell protective mechanisms to survive mitochondrial stress.
Sex, Specimen part
View SamplesAnalysis of in vivo antigen-specific (LCMV-specific, SMARTA TCR transgenic) follicular helper CD4 T cells (CXCR5high),versus non-follicular helper CD4 T cells (CXCR5low), eight days after viral infection. A paper including data analysis of these experiments has been accepted for publication (Robert J. Johnston et al. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of follicular helper CD4 T cell differentiation).
Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation.
Specimen part
View SamplesMRL/Faslpr mice is a lupus prone strain that exhibits lupus disease features at 12-16 weeks of age, including high-titer circulating anti-DNA antibodies, splenomegaly, lymphadnopathy, skin lesions, and IgG deposits in the kidney. At 16-24 weeks of age, CD4+ B220- CD44+ T cells were sorted into three populations based on the expression of two cell surface molecules, CD62L and PSGL1. CD62Lhi PSGL1hi, CD62Llo PSGL1hi, and CD62Llo PSGL1lo CD4+ T cells were isolated directly ex vivo. There was no treatment given to the animals. Naive (CD62Lhi CD44lo) CD4+ B220- T cells were isolated from young 6-8 week old female mice for comparison.
In vivo regulation of Bcl6 and T follicular helper cell development.
Specimen part
View SamplesThe goal of this study was to identify the molecular characteristics and putative markers distinguishing IL-10eGFP+CD138hi and IL-10eGFP-CD138hi plasmocytes. To this end, IL-10eGFP B-green mice were challenged intravenously with Salmonella typhimurium (strain SL7207, 10e7 CFU), and IL-10eGFP+CD138hi as well as IL-10eGFP-CD138hi plasmocytes were isolated from the spleen on the next day. For this, single cell suspensions were prepared, cells were treated with Fc block (10 g/ml, anti-CD16/CD32, clone 2.4G2), and then stained with an antibody against CD138 conjugated to PE (1/400; from BD Pharmingen) followed by incubation with anti-PE microbeads (Miltenyi Biotech). CD138+ cells were then enriched on Automacs (Miltenyi Biotech) using the program possel_d2. Cells were then stained with anti-CD19-PerCP, anti-CD138-PE, and antibodies against CD11b, CD11c, and TCR conjugated to APC as a dump channel to exclude possible contaminants. DAPI was added to exclude dead cells. Live IL-10eGFP+CD138hi and IL-10eGFP-CD138hi cells were subsequently isolated on a cell sorter. The purity of the samples was always above 98%. This led to the identification of LAG-3 as a cell surface receptor specifically expressed on IL-10eGFP+CD138hi cells but not on IL-10eGFP-CD138hi cells.
LAG-3 Inhibitory Receptor Expression Identifies Immunosuppressive Natural Regulatory Plasma Cells.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
E2f8 mediates tumor suppression in postnatal liver development.
Age, Specimen part
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