BGI Group (Japan)

The 15 species of small carnivorous marsupials that comprise the genus Antechinus exhibit semelparity, a rare life-history strategy where death occurs after one breeding season. Antechinus males, but not females, age rapidly (demonstrate organismal senescence) during the breeding season and show promise as new animal models of ageing. Some antechinus species are also threatened or endangered. Here, we report chromosome-level genomes of the yellow-footed antechinus Antechinus flavipes. The genome assembly has a total length of 3.2 Gb with a contig N50 of 51.8 Mb and a scaffold N50 of 636.7 Mb. We anchored and oriented 99.7% of the assembly on seven pseudochromosomes and found that repetitive DNA sequences occupy 51.8% of the genome. Draft genome assemblies of three related species in the subfamily Phascogalinae, two additional antechinus species (A. argentus and A. arktos) and the iteroparous sister species Murexia melanurus were also generated. Preliminary demographic analysis supports the hypothesis that climate change during the Pleistocene isolated species in Phascogalinae and shaped their population size. A transcriptomic profile across the A. flavipes breeding season allowed us to identify genes associated with aspects of the male die-off. The chromosome-level A. flavipes genome provides a steppingstone to understanding an enigmatic life-history strategy and a resource to assist the conservation of antechinuses.

High-resolution spatial transcriptomics (ST) data provide valuable insights into the molecular dynamics underlying complex biological processes. However, their widespread application remains limited due to high costs and technical challenges. Here, we present PRTS (Pathology-driven Reconstruction of Transcriptomic States), a novel framework that predicts single-cell-resolution ST data directly from histological images. Our results demonstrated that PRTS generated transcriptomic profiles for about 60,000 analyzable cell tiles per tissue section, representing an approximately 27-fold increase in analytical units compared to conventional ST spots and remarkably enhancing spatial resolution. Notably, PRTS achieves accurate cell-level transcriptomic predictions using only hematoxylin-and-eosin-stained tissue images. This method transforms costly ST technologies into a practical and scalable tool, offering a cost-efficient solution for comprehensive ST profiling in hematoxylin-and-eosin-based disease research.

The efficacy of chemotherapy depends partly on the ability to induce anti-tumor immunity. A better understanding of how different chemotherapy modes mediate antitumor immune responses could provide insights for developing optimized treatment modalities. Here, we demonstrated that metronomic chemotherapy, a mode of frequent and regular administration of chemotherapeutic drugs at lower doses, induced robust CD8+ T cell-dependent anti-tumor immune memory by modulating activity of mature regulatory dendritic cells (mregDCs). Mechanistically, by imposing more frequent stress on tumor cells, metronomic chemotherapy induced sustained activation of ATF4, leading to metabolic reprogramming of tumor cells and enhanced asparagine (Asn) release into the tumor microenvironment. Functioning as a ligand, Asn directly bound to AXL on mregDCs, inhibiting AXL kinase activity and downregulating PD-L1 expression. Consequently, mregDCs with reduced PD-L1 expression fostered the generation of more memory-like CD8+ T cells during their interactions. Overall, this study unveils critical biological events driving antitumor immune memory formation under therapeutic stress and provides a rationale for optimizing chemotherapy modalities.

Abstract Numerous studies have investigated the risk factors of Alzheimer’s disease (AD), however, AD- risk factors related miRNAs were rarely reported. In this study, AD- risk factor related miRNAs of 119 Chinese individuals (47 AD patients and 62 cognitively normal controls) were investigated. The results showed that education, tea consumption, leisure activity, and social connection were low Body Mass Index (BMI), depression, and smoking were potentially risk factors for AD patients. Moreover, we screened exosome microRNAs (miRNAs) for the aforementioned lifestyle-related factors. Canonical correlation analyses revealed that our clinical observations were correlated with the miRNA expression profile for education, depression, leisure activity, and social connection. Furthermore, we predicted the targets of differentially expressed miRNAs and found that many of them were reported to be involved in the generation and clearance of Amyloid-beta (Aβ), important molecules related to cognition, and disease-activated microglia response to AD. Our results indicated that certain education and depression factors can contribute to AD progression by modulating miRNA expression, implying that preventive interventions might alter AD progression in Chinese patients.

Analysis of transcription factors and chromatin modifications at the genome-wide level provides insights into gene regulatory processes, such as transcription, cell differentiation and cellular response. Chromatin immunoprecipitation is the most popular and powerful approach for mapping chromatin, and other enzyme-tethering techniques have recently become available for living cells. Among these, CUT&Tag is a relatively novel chromatin profiling method that has rapidly gained popularity in the field of epigenetics since 2019. It has also been widely adapted to map chromatin modifications and TFs in different species, illustrating the association of these chromatin epitopes with various physiological and pathological processes. Scalable single-cell CUT&Tag can be combined with distinct platforms to distinguish cellular identity, epigenetic features and even spatial chromatin profiling. In addition, CUT&Tag has been developed as a strategy for joint profiling of the epigenome, transcriptome or proteome on the same sample. In this review, we will mainly consolidate the applications of CUT&Tag and its derivatives on different platforms, give a detailed explanation of the pros and cons of this technique as well as the potential development trends and applications in the future.

The human gut microbiome, an essential component of the human digestive tract, is influenced by various elements including geographical location, ethnic background, dietary patterns, and genetic makeup. Geographical location, in particular, plays a significant role, as different regions in China exhibit distinct and unique bacterial groups. Furthermore, the impact of ethnicity on the composition of the gut microbiota should not be overlooked. In China, with its 56 ethnic subgroups, there exists an ethnic-specific clustering of gut microbiota, which contributes to a diverse range of microbial resources due to the presence of numerous minority groups. The relationship between gut microbiota and various diseases is an increasingly investigated area. Ethnic-specific gut microbiota can result in differences in disease incidence, and individuals from different ethnic groups may display variations in their gut microbiota when experiencing the same disease. The objective of this study is to present a comprehensive overview of the distinctive gut microbiome profiles across various regions and ethnic groups within China. This research highlights the unique characteristics of the gut microbiome among these minority populations and investigates the correlations between specific gut microbes and associated health conditions, a subject that remains underexplored in the current literature. This information will provide a basis for personalized medicine and the development of disease diagnostic models utilizing gut microbiota as biomarkers, thereby enabling more effective treatment plans and health management strategies.