Analysis of the human monocyte-derived macrophage transcriptome and response to lipopolysaccharide provides new insights into genetic aetiology of inflammatory bowel disease

The FANTOM5 consortium utilised cap analysis of gene expression (CAGE) to provide an unprecedented insight into transcriptional regulation in human cells and tissues. In the current study, we have used CAGE-based transcriptional profiling on an extended dense time course of the response of human monocyte-derived macrophages grown in macrophage colony-stimulating factor (CSF1) to bacterial lipopolysaccharide (LPS). We propose that this system provides a model for the differentiation and adaptation of monocytes entering the intestinal lamina propria. The response to LPS is shown to be a cascade of successive waves of transient gene expression extending over at least 48 hours, with hundreds of positive and negative regulatory loops. Promoter analysis using motif activity response analysis (MARA) identified some of the transcription factors likely to be responsible for the temporal profile of transcriptional activation. Each LPS-inducible locus was associated with multiple inducible enhancers, and in each case, transient eRNA transcription at multiple sites detected by CAGE preceded the appearance of promoter-associated transcripts. LPS-inducible long non-coding RNAs were commonly associated with clusters of inducible enhancers. We used these data to re-examine the hundreds of loci associated with susceptibility to inflammatory bowel disease (IBD) in genome-wide association studies. Loci associated with IBD were strongly and specifically (relative to rheumatoid arthritis and unrelated traits) enriched for promoters that were regulated in monocyte differentiation or activation. Amongst previously-identified IBD susceptibility loci, the vast majority contained at least one promoter that was regulated in CSF1-dependent monocyte-macrophage transitions and/or in response to LPS. On this basis, we concluded that IBD loci are strongly-enriched for monocyte-specific genes, and identified at least 134 additional candidate genes associated with IBD susceptibility from reanalysis of published GWA studies. We propose that dysregulation of monocyte adaptation to the environment of the gastrointestinal mucosa is the key process leading to inflammatory bowel disease

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Achievements and prospects in breeding for rhizomania resistance in sugar beet

Economic viability of a sugar beet crop largely depends on its successful protection against rhizomania, a most devastating disease that causes severe losses in root yield, sucrose content and quality. Rhizomania disease is caused by Beet necrotic yellow vein virus (BNYVV), a virus present in most sugar beet growing regions being vectored by the widely spread soil borne protoctist Polymyxa betae Keskin. The only prac- tical means to control the disease is the use of genetically resistant varieties and, to date, such resistance is mainly based on a dominant gene (Rz1) that when present confers a sufficiently high level of protec- tion against BNYVV. However, the emergence of virus strains capable of compromising the resistance employed in commercial varieties as well as a possible spread of more pathogenic isolates threatens crop’s protection efficiency in the future. All these point to the necessity for exploiting new and more effective genetic sources of rhizomania resistance, both by classical and molecular breeding approaches, a practice that is being pursued by the relevant breeding firms. This article critically reviews the various issues related to the disease and its management and particularly to the ones pertaining to pathogen genetic diversity, types of genetic resistance currently employed, as well as to novel biotechnological approaches aiming at the development of better resisting cultivars

Differential expression of heat shock protein genes in sorghum (Sorghum bicolor L.) genotypes under heat stress

Various types of sorghum were subjected to thermal stress to reveal the mode of expression of genes of the heat shock protein (hsp) family. In silico sequence determination of hsp genes in related cereal species led to the selection of appropriate primers for PCR amplification of a segment corresponding to the hsp90 gene from sorghum. Deduced sequence information allowed the design of gene specific primers for quantification of hsp90 gene expression by means of real-time quantitative polymerase chain reaction (RT-qPCR). Fourteen days-old plants were exposed to a temperature of 47°C for a time period ranging from 10 to 180 min. Total RNA was extracted from stressed and control plants and subjected to reverse transcription and RT-qPCR analysis. The actin gene was used as an internal standard. Gene expression was assessed by using cDNA from all types of plant material and for all the different durations of heat stress exposure. Data from RT-qPCR analyses were analyzed using REST software. The highest level of hsp90 gene expression was realized upon exposure to heat for either 60 or 30 min, while expression levels differed among the genotypes studied. In addition, overall levels of hsp90 gene expression were significantly different among varieties tested. Information of such genotypic variation in expression levels of hsp90 gene under heat stress, coupled with related field performance data, could potentially be exploited in breeding programs

Unravelling mononuclear phagocyte heterogeneity

When Ralph Steinman and Zanvil Cohn first described dendritic cells (DCs) in 1973 it took many years to convince the immunology community that these cells were truly distinct from macrophages. Almost four decades later, the DC is regarded as the key initiator of adaptive immune responses; however, distinguishing DCs from macrophages still leads to confusion and debate in the field. Here, Nature Reviews Immunology asks five experts to discuss the issue of heterogeneity in the mononuclear phagocyte system and to give their opinion on the importance of defining these cells for future research