Clinical efficacy of treatments against non-obstructive azoospermia (NOA), which affects 1% of men, are currently limited by the incomplete understanding of NOA pathogenesis and normal spermatogenic microenvironment. Here, we profile >80,000 human testicular single-cell transcriptomes from 10 healthy donors spanning the range from infant to adult and 7 NOA patients. We show that Sertoli cells, which form the scaffold in the testicular microenvironment, are severely damaged in NOA patients and identify the roadmap of Sertoli cell maturation. Notably, Sertoli cells of patients with congenital causes (Klinefelter syndrome and Y chromosome microdeletions) are mature, but exhibit abnormal immune responses, while the cells in idiopathic NOA (iNOA) are physiologically immature. Furthermore, we find that inhibition of Wnt signaling promotes the maturation of Sertoli cells from iNOA patients, allowing these cells to regain their ability to support germ cell survival. We provide a novel perspective on the development of diagnostic methods and therapeutic targets for NOA.

Background Akkermansia muciniphila is one of the most dominant bacteria that resides on the mucus layer of intestinal tract and plays key role in human health, however, little is known about its genomic content.ResultsHerein, we for the first time characterized the genomic architecture of A. muciniphila based on whole-genome sequencing, assembling, and annotating of 39 isolates derived from human and mouse feces. We revealed a flexible open pangenome of A. muciniphila currently consisting of 5644 unique proteins. Phylogenetic analysis identified three species-level A. muciniphila phylogroups exhibiting distinct metabolic and functional features. Based on the comprehensive genome catalogue, we reconstructed 106 newly A. muciniphila metagenome assembled genomes (MAGs) from available metagenomic datasets of human, mouse and pig gut microbiomes, revealing a transcontinental distribution of A. muciniphila phylogroups across mammalian gut microbiotas. Accurate quantitative analysis of A. muciniphila phylogroups in human subjects further demonstrated its strong correlation with body mass index and anti-diabetic drug usage. Furthermore, we found that, during their mammalian gut evolution history, A. muciniphila acquired extra genes, especially antibiotic resistance genes, from symbiotic microbes via recent lateral gene transfer.ConclusionsThe genome repertoire of A. muciniphila provided insights into population structure, evolutionary and functional specificity of this significant bacterium.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4195-3) contains supplementary material, which is available to authorized users.

Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10−10), 3p22.1 (rs67311347, P=2.5 × 10−8), 3q26.2 (rs10936602, P=8.8 × 10−9), 8p21.3 (rs2241261, P=5.8 × 10−9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10−8), 11q22.3 (rs74911261, P=2.1 × 10−10) and 14q24.2 (rs4903064, P=2.2 × 10−24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.

BackgroundMeat quality is an important economic trait in chickens. To identify loci and genes associated with meat quality traits, we conducted a genome-wide association study (GWAS) of F2 populations derived from a local Chinese breed (Beijing-You chickens) and a commercial fast-growing broiler line (Cobb-Vantress).ResultsIn the present study, 33 association signals were detected from the compressed mixed linear model (MLM) for 10 meat quality traits: dry matter in breast muscle (DMBr), dry matter in thigh muscle (DMTh), intramuscular fat content in breast muscle (IMFBr), meat color lightness (L*) and yellowness (b*) values, skin color L*, a* (redness) and b* values, abdominal fat weight (AbFW) and AbFW as a percentage of eviscerated weight (AbFP). Relative expressions of candidate genes identified near significant signals were compared using samples of chickens with High and Low phenotypic values. A total of 14 genes associated with IMFBr, meat color L*, AbFW, and AbFP, were differentially expressed between the High and Low phenotypic groups. These genes are, therefore, prospective candidate genes for meat quality traits: protein tyrosine kinase (TYRO3) and microsomal glutathione S-transferase 1 (MGST1) for IMFBr; collagen, type I, alpha 2 (COL1A2) for meat color L*; and RET proto-oncogene (RET), natriuretic peptide B (NPPB) and sterol regulatory element binding transcription factor 1 (SREBF1) for the abdominal fat (AbF) traits.ConclusionsBased on the association signals and differential expression of nearby genes, 14 candidate loci and genes for IMFBr, meat L* and b* values, and AbF are identified. The results provide new insight into the molecular mechanisms underlying meat quality traits in chickens.