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A distinct feature of development in the simple eukaryote Dictyostelium discoideum is an aggregative transition from a unicellular to a multicellular phase. Using genome-wide transcriptional analysis we show that this transition is accompanied by a dramatic change in the expression of more than 25% of the genes in the genome. We also show that the transcription patterns of these genes are not sensitive to the strain or the nutritional history, indicating that Dictyostelium development is a robust physiological process that is accompanied by stereotypical transcriptional events. Analysis of the two differentiated cell types, spores and stalk cells, and their precursors revealed a large number of differentially expressed genes as well as unexpected patterns of gene expression, which shed new light on the timing and possible mechanisms of cell-type divergence. Our findings provide new perspectives on the complexity of the developmental program and the fraction of the genome that is regulated during development.

Purpose:Mice deficient in PD-1, an immuno-inhibitory co-receptor, develop dilated cardiomyopathy (DCM) with high-titer autoantibodies reactive to cardiac troponin I (cTnI). This study examined the hemodynamics and role of anti-cTnI antibodies (Ab) in PD-1 deficient mice with DCM. Method and Result:The left ventricular (LV) pressure-volume relationship (PVR) was determined in vivo. Contractility was decreased and enddiastolic volume (EDV) increased in PD-1−/−compared with PD-1+/−mice. To examine the role of anti-cTnI Ab, wild type BALB/c mice were inoculated with anti-cTnI monoclonal Ab. At 12 weeks, the hearts of anti-cTnI Ab-treated mice displayed decreased contractility and increased EDV. Normalized end-systolic elastance was significantly lower in anti-cTnI Ab-treated (5.27 ± 0.82, n=5) than in control IgG-treated mice (17.36 ± 4.63 mmHg/μL×100mg, n=5, P < 0.05). EDV (24.8 ± 1.4 vs 19.2 ± 0.7 μL in control), and end-diastolic pressure were significantly higher in the anti-cTnI Ab-treated than in IgG-treated mice (P < 0.05). These data indicate that the long-term administration of anti-cTnI Ab caused LV dilatation by decreasing contractility. We also studied the electrophysiologic effects of anti-cTnI Ab on isolated cardiomyocytes in vitro. The addition of monoclonal Ab against cTnI increased the Ca2+current 1.5 fold compared to the control IgG group. Conclusion:These observations suggest that anti-cTnI Ab are responsible for systolic dysfunction and LV dilatation by enhancing the Ca2+current in cardiomyocytes.