CD127 imprints functional heterogeneity to diversify monocyte responses in inflammatory diseases

Inflammatory monocytes are key mediators of acute and chronic inflammation; yet, their functional diversity remains obscure. Single-cell transcriptome analyses of human inflammatory monocytes from COVID-19 and rheumatoid arthritis patients revealed a subset of cells positive for CD127, an IL-7 receptor subunit, and such positivity rendered otherwise inert monocytes responsive to IL-7. Active IL-7 signaling engaged epigenetically coupled, STAT5-coordinated transcriptional programs to restrain inflammatory gene expression, resulting in inverse correlation between CD127 expression and inflammatory phenotypes in a seemingly homogeneous monocyte population. In COVID-19 and rheumatoid arthritis, CD127 marked a subset of monocytes/macrophages that retained hypoinflammatory phenotypes within the highly inflammatory tissue environments. Furthermore, generation of an integrated expression atlas revealed unified features of human inflammatory monocytes across different diseases and different tissues, exemplified by those of the CD127high subset. Overall, we phenotypically and molecularly characterized CD127-imprinted functional heterogeneity of human inflammatory monocytes with direct relevance for inflammatory diseases.

Integrated view and comparative analysis of baseline protein expression in mouse and rat tissues

The increasingly large amount of public proteomics data enables, among other applications, the combined analyses of datasets to create comparative protein expression maps covering different organisms and different biological conditions. Here we have reanalysed public proteomics datasets from mouse and rat tissues (14 and 9 datasets, respectively), to assess baseline protein abundance. Overall, the aggregated dataset contains 23 individual datasets, which have a total of 211 samples coming from 34 different tissues across 14 organs, comprising 9 mouse and 3 rat strains, respectively. We compared protein expression between the different organs, including the distribution of proteins across them. We also performed gene ontology and pathway enrichment analyses to identify organ-specific enriched biological processes and pathways. As a key point we carried out a comparative analysis of protein expression between mouse, rat and human tissues. We observed a high level of correlation of protein expression among orthologs between all three species in brain, kidney, heart and liver samples. Finally, it should be noted that protein expression results have been integrated into the resource Expression Atlas for widespread dissemination.

CHEK1: a hub gene related to poor prognosis for lung adenocarcinoma

Aim: The study aims to pinpoint hub genes and investigate their functions in order to gain insightful understandings of lung adenocarcinoma (LUAD). Methods: Bioinformatic approaches were adopted to investigate genes in databases including Gene Expression Omnibus, WebGestalt, STRING and Cytoscape, GEPIA2, Oncomine, Human Protein Atlas, TIMER2.0, UALCAN, cBioPortal, TargetScanHuman, OncomiR, ENCORI, Kaplan–Meier plotter, UCSC Xena, European Molecular Biology Laboratory – European Bioinformatics Institute Single Cell Expression Atlas and CancerSEA. Results: Five hub genes were ascertained. CHEK1 was overexpressed in a range of cancers, including LUAD. Promoter methylation, amplification and miRNA regulation might trigger CHEK1 upregulation, signaling poor prognosis. CHEK1 with its coexpressed genes were enriched in the cell cycle pathway. Intratumor heterogeneity of CHEK1 expression could be observed. Cell clusters with CHEK1 expression were more prone to metastasis and epithelial-to-mesenchymal transition. Conclusion: CHEK1 might potentially act as a prognostic biomarker for LUAD.

A population based expression atlas provides insights into disease resistance and other physiological traits in cassava (Manihot esculenta Crantz)

Cassava, a food security crop in Africa, is grown throughout the tropics and subtropics. Although cassava can provide high productivity in suboptimal conditions, the yield in Africa is substantially lower than in other geographies. The yield gap is attributable to many challenges faced by cassava in Africa, including susceptibility to diseases and poor soil conditions. In this study, we carried out 3’RNA sequencing on 150 accessions from the National Crops Resources Research Institute, Uganda for 5 tissue types, providing population-based transcriptomics resources to the research community in a web-based queryable cassava expression atlas. Differential expression and weighted gene co-expression network analysis were performed to detect 8820 significantly differentially expressed genes (DEGs), revealing similarity in expression patterns between tissue types and the clustering of detected DEGs into 18 gene modules. As a confirmation of data quality, differential expression and pathway analysis targeting cassava mosaic disease (CMD) identified 27 genes observed in the plant–pathogen interaction pathway, several previously identified CMD resistance genes, and two peroxidase family proteins different from the CMD2 gene. Present research work represents a novel resource towards understanding complex traits at expression and molecular levels for the development of resistant and high-yielding cassava varieties, as exemplified with CMD.

R code and downstream analysis objects for the scRNA-seq atlas of human breast spanning normal, preneoplastic and tumorigenic states

Breast cancer is a common and highly heterogeneous disease. Understanding the cellular diversity in the mammary gland and its surrounding micro-environment across different states can provide insight into the cancer development in human breast. Recently, a large-scale single-cell RNA expression atlas was constructed of the human breast spanning normal, preneoplastic and tumorigenic states. Single-cell expression profiles of nearly 430,000 cells were obtained from 69 distinct surgical tissue specimens from 55 patients. This article extends the study by providing downstream processed R data objects, complete cell annotation and R code to reproduce all the analyses. Details of all the bioinformatic analyses that produced the results described in the study are provided.

Marchantia polymorpha gene expression atlas reveals the hierarchy of abiotic stress responses and conservation of diurnal gene expression

Abiotic stress has a dramatic impact on ecosystems and the yield of crops, and global warming will likely result in more frequent and intense stresses. However, due to the complexity of the underlying signalling pathways and the fact that stresses often occur in combinations in nature, our knowledge of how plants acclimatize to abiotic stress is still lacking. Here, we used a plant with minimal regulatory network redundancy, Marchantia polymorpha, to study how seven abiotic stresses alone and in combination affect the phenotype, gene expression, and activity of biological pathways. Worryingly, we see no evidence of conservation of gene expression to abiotic stress between model organisms, suggesting that each species develops unique strategies to cope with abiotic stress. Interestingly, we observed that certain stresses are able to suppress others, while specific combinations can elucidate novel transcriptomic responses. Finally, we provide two online databases to study abiotic stress responses and diurnal gene expression data in Marchantia.

A chelicerate Wnt gene expression atlas: novel insights into the complexity of arthropod Wnt-patterning

The Wnt genes represent a large family of secreted glycoprotein ligands that date back to early animal evolution. Multiple duplication events generated a set of 13 Wnt families of which 12 are preserved in protostomes. Embryonic Wnt expression patterns (Wnt-patterning) are complex, representing the plentitude of functions these genes play during development. Here, we comprehensively investigated the embryonic expression patterns of Wnt genes from three species of spiders covering both main groups of true spiders, Haplogynae and Entelegynae, a mygalomorph species (tarantula), as well as a distantly related chelicerate outgroup species, the harvestman Phalangium opilio. All spiders possess the same ten classes of Wnt genes, but retained partially different sets of duplicated Wnt genes after whole genome duplication, some of which representing impressive examples of sub- and neo-functionalization. The harvestman, however, possesses a more complete set of 11 Wnt genes but with no duplicates. Our comprehensive data-analysis suggests a high degree of complexity and evolutionary flexibility of Wnt-patterning likely providing a firm network of mutational protection. We discuss the new data on Wnt gene expression in terms of their potential function in segmentation, posterior elongation, and appendage development and critically review previous research on these topics. We conclude that earlier research may have suffered from the absence of comprehensive gene expression data leading to partial misconceptions about the roles of Wnt genes in development and evolution.