Recent studies have shown that tissue macrophages (MF) arise from embryonic progenitors of the yolk sac (YS) and fetal liver and colonize the tissues before birth. Further studies have proposed that developmentally distinct tissue MF can be identified based on the differential expression of F4/80 and CD11b, but whether a characteristic transcriptional profile exists is largely unknown. Here, we established an inducible fate mapping system that facilitated the identification of A2 progenitors of the YS as source of F4/80hi but not CD11bhi MF. Large-scale transcriptional profiling of MF precursors from the YS until adulthood allowed the description of a complex MF pedigree. We further identified a distinct molecular signature of F4/80hi and CD11bhi MF and found that Irf8 was vital for MF maturation and the innate immune response. Our data provide new cellular and molecular insights into the origin and developmental pathways of tissue MF.
Transcriptome-based profiling of yolk sac-derived macrophages reveals a role for Irf8 in macrophage maturation.
Specimen part
View SamplesWe study differences in gene expression between Populus P35S::BL (BL-oe) lines and control, affecting plant growth and differentiation, and dormancy. We used microarrays to detail the global program of gene expression underlying morphological and developmental changes droved by overexpression of BL gene.
BIG LEAF is a regulator of organ size and adventitious root formation in poplar.
Specimen part
View SamplesThe aim of this analysis was to investigate the changes in the gene expression pattern of ex vivo cultured wildtype murine osteoclasts during the course of osteoclastogenic differentiation.
The Lysosomal Protein Arylsulfatase B Is a Key Enzyme Involved in Skeletal Turnover.
Sex, Specimen part
View SamplesLong non-coding RNAs (lncRNAs) contribute to (patho)physiological processes in the heart. Aging is the major risk factor for cardiovascular disease and cardiomyocyte apoptosis is an underlying cause for age-related cardiac dysfunction. RNA sequencing of cardiomyocytes from young and aged mouse hearts revealed several aging-regulated lncRNAs. An siRNA screen for caspase activity identified the aging-regulated lncRNA Sarrah (ENSMUST00000140003) as anti-apoptotic, which we confirmed in human cells (human SARRAH is annotated as OXCT1-AS1). Importantly, human engineered heart tissue showed impaired contractile force development upon SARRAH knockdown compared with controls. Computational prediction of RNA-DNA triple helix formation showed that SARRAH may directly bind the promoters of genes downregulated after SARRAH silencing, which mainly consist of cell survival genes. Indeed, nuclear magnetic resonance spectroscopy confirmed RNA-DNA triple helix formation and cardiomyocytes lacking the triple helix-forming domain of Sarrah showed an increase in apoptosis. One of the key direct SARRAH targets is NRF2, an anti-oxidant transcription factor. Restoration of NRF2 levels after SARRAH silencing partially rescues the reduction in cell viability. RNA affinity purification mass spectrometry analysis identified CRIP2 as main protein interaction partner. Furthermore, SARRAH associates with acetyltransferase p300 and acetylated histone H3K27. Finally, Sarrah was also profoundly downregulated after acute myocardial infarction (AMI) in mice. Adeno-associated virus-mediated overexpression of Sarrah in mice showed better recovery of cardiac contractile function after AMI compared to control mice, as measured by echocardiography and magnetic resonance imaging, consistent with a decrease in cardiomyocyte cell death and an increase in endothelial cell proliferation. In summary, we identified the anti-apoptotic evolutionary conserved lncRNA Sarrah, which is downregulated by aging, as a pivotal regulator of cardiomyocyte survival. Sarrah overexpression has beneficial effects on AMI recovery highlighting it as a potential therapeutic approach against heart failure.
Aging-regulated anti-apoptotic long non-coding RNA Sarrah augments recovery from acute myocardial infarction.
Specimen part
View SamplesA growing body of evidence suggests that the vasoactive peptides endothelins (ETs) and their receptors (primarily the ETB receptor) are contributors to neurodegeneration in glaucoma. However, ETs actions in retinal ganglion cells (RGCs) are not fully understood. The purpose of this study was to determine ETs effects on gene expression in primary RGCs.
Endothelin-Mediated Changes in Gene Expression in Isolated Purified Rat Retinal Ganglion Cells.
Specimen part
View SamplesWe studied differences in gene expression between Populus P35S::EBB1 lines and control, affecting plant growth and differentiation, and dormancy. We used microarrays to detail the global program of gene expression underlying morphological and developmental changes driven by overexpression of the EBB1 gene.
EARLY BUD-BREAK 1 (EBB1) is a regulator of release from seasonal dormancy in poplar trees.
Specimen part
View SamplesWe study gene expression Populus amiEBB1 lines affecting dormancy. We used microarrays to detail the global program of gene expression underlying morphological and developmental changes droved by expression of artifical micro RNA (ami) targeting EBB1 gene.
EARLY BUD-BREAK 1 (EBB1) is a regulator of release from seasonal dormancy in poplar trees.
Specimen part
View SamplesWe study the effect of nitrogen limitation on the growth and development of poplar roots. We used microarrays to detail the global program of gene expression underlying morphological and developmental changes driven by low nitrogen in the growth media. We report the effect of nitrogen limitation on the growth and development of poplar roots. Low nitrogen concentration led to increased root elongation followed by lateral root proliferation and finally increased root biomass. These morphological responses correlated with high and specific activation of genes encoding regulators of cell cycle and enzymes involved in cell wall biogenesis, growth and remodeling. Comparative analysis of poplar and Arabidopsis root transcriptomes under nitrogen deficiency indicated many similarities and diversification in the response in the two species. A reconstruction of genetic regulatory network (GRN) analysis revealed a sub-network centered on a PtaNAC1-like transcription factor. Consistent with the GRN predictions, root-specific upregulation of PtaNAC1 in transgenic poplar plants increased root biomass and led to significant changes in the expression of the connected genes specifically under low nitrogen. PtaNAC1 and its regulatory miR164 showed inverse expression profiles during response to LN, suggesting of a micro RNA mediated attenuation of PtaNAC1 transcript abundance in response to nitrogen deprivation.
Nitrogen deprivation promotes Populus root growth through global transcriptome reprogramming and activation of hierarchical genetic networks.
Specimen part, Treatment, Time
View SamplesGenomewide analysis of gene expression associated with Tcof1 in mouse neuroblastoma. NB N1E-115 cells with wildtype, overexpression, knockdown of Tcof1.
Genomewide analysis of gene expression associated with Tcof1 in mouse neuroblastoma.
No sample metadata fields
View SamplesThe tetracycline antibiotics are widely used in biomedical research as mediators of inducible gene expression systems. Despite many known effects of tetracyclines on mammalian cells -- including inhibition of the mitochondrial ribosome -- there have been few reports on potential off-target effects at concentrations commonly used in inducible systems. Here, we report that in human cell lines, commonly used concentrations of doxycycline change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption. We also show that these concentrations are sufficient to slow proliferation and alter cell cycle progression in vitro. These findings suggest that researchers using doxycycline in inducible expression systems should design appropriate controls to account for potential confounding effects of the drug on cellular metabolism.
Doxycycline alters metabolism and proliferation of human cell lines.
Specimen part, Cell line, Treatment
View Samples