ING1b and GADD45a are nuclear proteins involved in the regulation of cell growth, apoptosis and DNA repair. We previously found that ING1b is required to target GADD45a-mediated active DNA-demethylation via TET1 to specific loci. In order to study the impact of ING1-GADD45a on gene expression, we compared the expression profile of wildtype mouse embryonic fibroblasts (MEFs) with Ing1- and Gadd45a- single- or double-knockout (DKO) MEFs. Overall design: Gene expression profiling in all 4 genotypes of undifferentiated MEFs in triplicates.
Impaired DNA demethylation of C/EBP sites causes premature aging.
Sex, Specimen part, Cell line, Subject
View SamplesInnate and adaptive immune cells modulate heart failure pathogenesis during viral myocarditis, yet their identity and functions remain poorly defined. In this study we characterized the phenotype, life-cycle and function of different conventional dendritic cells (cDC) populations in the heart, with focus on the 2 major subsets (CD103+ and CD11b+), which differentially rely on local proliferation and precursor recruitment to maintain tissue residency. Following viral infection of the myocardium, cDCs accumulate in the heart coincident with monocyte infiltration and loss of resident reparative embryonic-derived cardiac macrophages. cDC depletion abrogates antigen-specific CD8+ T cell proliferative expansion, transforming subclinical cardiac injury to overt heart failure. Importantly, these effects are mediated by BATF3-dependent CD103+ cDCs. Collectively, our findings definitively identify resident cardiac cDC subsets, define their origins, and implicate an essential role for CD103+ cDCs in antigen-specific T cell responses during viral myocarditis.
A CD103<sup>+</sup> Conventional Dendritic Cell Surveillance System Prevents Development of Overt Heart Failure during Subclinical Viral Myocarditis.
Sex, Specimen part
View SamplesNormal arteries contain a large population of tissue resident macrophages (M). Their origins, as well as the mechanisms that sustain them during homeostasis and disease, however, are poorly understood. Gene expression profiling, we show, identifies arterial M as a distinct population among tissue M. Ontologically, arterial M arise before birth, though CX3CR1-, Csf1r-, and Flt3-driven fate mapping approaches demonstrate M colonization occurs through successive contributions of yolk sac (YS) and conventional hematopoiesis. In adulthood, arterial M renewal is driven by local proliferation rather than monocyte recruitment from the blood. Proliferation sustains M not only during steady state conditions, but mediates their rebound after severe depletion following sepsis. Importantly, the return of arterial M to functional homeostasis after infection is rapid; repopulated M exhibit a transcriptional program similar to resting M and efficiently phagocytose bacteria. Collectively, our data provide a detailed framework for future studies of arterial M function in health and disease.
Self-renewing resident arterial macrophages arise from embryonic CX3CR1(+) precursors and circulating monocytes immediately after birth.
Sex, Specimen part
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