BGI Group (Japan)

Abstract Introduction Human skin serves as a dynamic habitat for a diverse microbiome, including a complex array of viruses whose diversity and roles are not fully understood. Objectives This study aims to enhance our understanding of this skin viral diversity through the construction of a detailed, non-redundant DNA viral reference catalog. Methods A total of 2,760 skin metagenomes from six published skin studies were collected. A skin virome catalog was constructed using methods independent of reference databases. Viral characteristics were identified through cross-cohort meta-analysis and used to characterize viral features across different skin environments. Results We identified 20,927 viral sequences, which clustered into 2,873 viral operational taxonomic units (vOTUs). Among these, 2,610 represent previously unrecorded viral sequences, uncovering a substantial breadth of viral diversity on human skin. The results also highlight significant differences in viral communities that are associated with varying skin microenvironments. The oily skin is enriched in Papillomaviridae ; the dry skin area is enriched in Autographiviridae , Inoviridae and Mitoviridae ; and the moist skin is enriched in Herelleviridae , indicating the adaptive nature of viruses. We also investigated the relationship between bacteriophages and bacteria on the skin surface. We found that skin bacteria such as Pseudomonas , Klebsiella , and Staphylococcus are infected by phages from the class Caudoviricetes . Conclusion This comprehensive skin DNA viral catalog significantly advances our understanding of the virome’s role within the skin ecosystem. The findings highlight the adaptive nature of viruses to different skin microenvironments and their interactions with resident bacteria. This catalog serves as a valuable resource for further epidemiological and therapeutic research, potentially leading to better management and treatment of skin conditions influenced by the skin’s virome.

Abstract Adaptive immunity, mediated by T and B cell responses, is essential for defending against infections and cancers while also being implicated in autoimmune diseases. Tracking T and B cell repertoires in situ at single-cell resolution is essential for understanding adaptive immune responses. To address the lack of tools for in situ single-cell T/BCR (XCR) sequencing, we developed Stereo-XCR-seq, an efficient strategy for retrieving and sequencing TCR and BCR from Stereo-seq cDNA libraries at subcellular resolution. Stereo-XCR-seq provides unbiased full-length XCR reads alongside spatial transcriptomics, enabling the identification of heterogeneous lymphoid aggregates with distinct clonal activities in cancers and inflammatory bowel disease (IBD). We identified plasma cell aggregates that differ from tertiary lymphoid structures (TLSs) in both transcriptomic profiles and clonal activities, with spatial positioning potentially mediating unique immune responses. Collectively, Stereo-XCR-seq enables in situ single-cell profiling of T and B cell clonal activities within tissue microenvironments, providing insights into lymphocyte adaption to environmental stimuli. This technology provides potential for advancing our understanding of tissue immunity and the development of therapeutic strategies for immune disorders.

Abstract Background: Setaria italica is the second-most widely planted species of millets in the world and an important model grain crop for the research of C4 photosynthesis and abiotic stress tolerance. Through three genomes assembly and annotation efforts, all genomes were based on next generation sequencing technology, which limited the genome continuity. Results: Here we report a high-quality whole-genome of new cultivar Huagu11, using single-molecule real-time sequencing and High-throughput chromosome conformation capture (Hi-C) mapping technologies. The total assembly size of the Huagu11 genome was 408.37 Mb with a scaffold N50 size of 45.89 Mb. Compared with the other three reported millet genomes based on the next generation sequencing technology, the Huagu11 genome had the highest genomic continuity. Intraspecies comparison showed about 94.97% and 94.66% of the Yugu1 and Huagu11 genomes, respectively, were able to be aligned as one-to-one blocks with four chromosome inversion. The Huagu11 genome contained approximately 19.43 Mb Presence/absence Variation (PAV) with 627 protein-coding transcripts, while Yugu1 genomes had 20.53 Mb PAV sequences encoding 737 proteins. Overall, 969,596 Single-nucleotide polymorphism (SNPs) and 156,282 insertion-deletion (InDels) were identified between these two genomes. The genome comparison between Huagu11 and Yugu1 should reflect the genetic identity and variation between the cultivars of foxtail millet to a certain extent. The Ser-626-Aln substitution in acetohydroxy acid synthase (AHAS) was found to be relative to the imazethapyr tolerance in Huagu11. Conclusions: A new improved high-quality reference genome sequence of Setaria italica was assembled, and intraspecies genome comparison determined the genetic identity and variation between the cultivars of foxtail millet. Based on the genome sequence, it was found that the Ser-626-Aln substitution in AHAS was responsible for the imazethapyr tolerance in Huagu11. The new improved reference genome of Setaria italica will promote the genic and genomic studies of this species and be beneficial for cultivar improvement.

Abstract BackgroundLong-term exposure to microgravity during spaceflight has adverse effects on human health including muscle atrophy, impaired immune function, and alterations in gut microbiome profile. Gut microorganisms influence a wide range of host biological processes, but their interactions with skeletal muscle and the immune system under microgravity are not known. MethodsRhesus macaques (Macaca mulatta) were subjected to -6° head-down tilted bed rest (HDBR) for 6 weeks. Fecal samples, skeletal muscle tissue, and peripheral blood mononuclear cells (PBMCs) were collected for metagenomic, metabolomic, and transcriptomic analyses respectively and further integrated for a multi-omics analysis.ResultsHDBR resulted in significantly altered taxon abundance in 1 class, 5 orders, 11 families, 55 genera, and 122 species of microbes. We also identified the significantly changed metabolites in atrophied muscles, including some crucial metabolites (such as L-alanine and L-carnitine) and hub metabolites (such as pyridoxamine and epinephrine) involved in energy metabolism. Transcriptomic analysis of PBMCs revealed genes related to leukocyte activation, differentiation, and interleukin-2 production that were differentially expressed as a result of HDBR exposure. By integrating multi-omics analysis, we identified 3 bacterial genera (Klebsiella, Kluyvera, and Bifidobacterium) that were closely associated with immune dysfunction and 5 (including Oligella, Sporosarcina, Citrobacter, Weissella, and Myroide) that were associated with abnormal metabolism of amino acids in atrophied muscles induced by HDBR. Of note, the reduced abundance of butyrate-producing colon bacteria Eubacterium, Roseburia and their cross-feeding bacteria Bifidobacteria may contribute to both the impaired immune function and muscle atrophy caused by HDBR.ConclusionsWe first reported the HDBR-associated changes in gut microbiota composition, metabolomics of skeletal muscle and transcripts of PBMCs in non-human primate. Particularly, we revealed the underlying microbiota-muscle and microbiota-immune interactions during simulated microgravity, implicating that modulation of gut microbiota may represent a new strategy in enhancing crewmembers’ health and safety during long-term space expeditions.