Induced mesenchymal stromal cells (iMSCs) derived from human pluripotent stem cells (PSCs) are attractive cells for regenerative medicine. However, the transcriptome of iMSCs and signature genes that can distinguish MSCs from fibroblasts and other cell types are rarely explored. In this study, we reported an optimized feeder-free method for the generation of iMSCs from human pluripotent stem cells. These iMSCs display a typical MSC morphology, express classic MSC markers (CD29, CD44, CD73, CD90, CD105, CD166), are negative for lymphocyte markers (CD11b, CD14, CD31, CD34, CD45, HLA-DR), and are potent for osteogenic and chondrogenic differentiation. Using genome-wide transcriptome profiling, we created an easily accessible transcriptome reference for the process of differentiating PSCs into iMSCs. The iMSC transcriptome reference revealed clear patterns in the silencing of pluripotency genes, activation of lineage commitment genes, and activation of mesenchymal genes during iMSC generation. All previously known positive and negative markers for MSCs were confirmed by our iMSC transcriptomic reference, and most importantly, gene classification and time course analysis identified 52 genes including FN1, TGFB1, TAGLN and SERPINE1, which showed significantly higher expression in MSCs (over 3 folds) than fibroblasts and other cell types. Taken together, these results provide a useful method and important resources for developing and understanding iMSCs in regenerative medicine.

Familial hypophosphatemic rickets (HR), the most common inherited form of rickets, is a group of inherited renal phosphate wasting disorders characterized by growth retardation, rickets with bone deformities, osteomalacia, poor dental development, and hypophosphatemia. The purpose of this study was to identify the genetic defect responsible for familial HR in a four-generation Chinese Han pedigree by exome sequencing and Sanger sequencing. Clinical features include skeletal deformities, teeth abnormalities, hearing impairments and variable serum phosphate level in patients of this family. A novel deletion mutation, c.1553delT (p.F518Sfs*4), was identified in the X-linked phosphate regulating endopeptidase homolog gene (PHEX). The mutation is predicted to result in prematurely truncated and loss-of-function PHEX protein. Our data suggest that exome sequencing is a powerful tool to discover mutation(s) in HR, a disorder with genetic and clinical heterogeneity. The findings may also provide new insights into the cause and diagnosis of HR, and have implications for genetic counseling and clinical management.

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized for its global prevalence and potential progression to more severe liver diseases such as non-alcoholic steatohepatitis (NASH). The gut microbiota plays a pivotal role in the pathogenesis of NAFLD, yet the detailed characteristics and ecological alterations of gut microbial communities during the progression from non-alcoholic fatty liver (NAFL) to NASH remain poorly understood. Methods: In this study, we conducted a comparative analysis of gut microbiota composition in individuals with NAFL and NASH to elucidate differences and characteristics. We utilized 16S rRNA sequencing to compare the intestinal gut microbiota among a healthy control group (65 cases), NAFL group (64 cases), and NASH group (53 cases). Random forest machine learning and database validation methods were employed to analyze the data. Results: Our findings indicate a significant decrease in the diversity of intestinal flora during the progression of NAFLD (p < 0.05). At the phylum level, high abundances of Bacteroidetes and Fusobacteria were observed in both NAFL and NASH patients, whereas Firmicutes were less abundant. At the genus level, a significant decrease in Prevotella expression was seen in the NAFL group (AUC 0.738), whereas an increase in the combination of Megamonas and Fusobacterium was noted in the NASH group (AUC 0.769). Furthermore, KEGG pathway analysis highlighted significant disturbances in various types of glucose metabolism pathways in the NASH group compared to the NAFL group, as well as notably compromised flavonoid and flavonol biosynthesis functions. The study uncovers distinct microbiota characteristics and microecological changes within the gut during the transition from NAFL to NASH, providing insights that could facilitate the discovery of novel biomarkers and therapeutic targets for NAFLD.

Postmenopausal osteoporosis is the most common type of osteoporosis in women. To date, little is known about their transcriptome signatures, although biomarkers from peripheral blood mononuclear cells are attractive for postmenopausal osteoporosis diagnoses. Here, we performed bulk RNA sequencing of 206 samples (124 postmenopausal osteoporosis and 82 normal samples) and described the clinical phenotypic characteristics of postmenopausal women. We then highlighted the gene set enrichment analyses between the extreme T-score group and the heathy control group, revealing that some immune-inflammatory responses were enhanced in postmenopausal osteoporosis, with representative pathways including the mitogen-activated protein kinase (NES = 1.6, FDR <0.11) pathway and B_CELL_RECEPTOR (NES = 1.69, FDR <0.15) pathway. Finally, we developed a combined risk prediction model based on lasso-logistic regression to predict postmenopausal osteoporosis, which combined eleven genes (PTGS2, CXCL16, NECAP1, RPS23, SSR3, CD74, IL4R, BTBD2, PIGS, LILRA2, MAP3K11) and three pieces of clinical information (age, procollagen I N-terminal propeptide, β isomer of C-terminal telopeptide of type I) and provided the best prediction ability (AUC = 0.97). Taken together, this study filled a gap in the large-scale transcriptome signature profiles and revealed the close relationship between immune-inflammatory responses and postmenopausal osteoporosis, providing a unique perspective for understanding the occurrence and development of postmenopausal osteoporosis.

African swine fever (ASF) is a lethal contagious viral disease of domestic pigs and wild boars caused by the African swine fever virus (ASFV). The pandemic spread of ASF has had serious effects on the global pig industry. Virus genome sequencing and comparison play an important role in tracking the outbreaks of the disease and tracing the transmission of the virus. Although more than 140 ASFV genome sequences have been deposited in the public databases, the genome-wide diversity of ASFV remains unclear. Here we prepared a curated dataset of ASFV genome sequences by filtering genomes with sequencing errors as well as duplicated genomes. A total of 123 ASFV genome sequences were included in the dataset, representing 10 genotypes collected between 1949 and 2020. Phylogenetic analysis based on whole-genome sequences provided high-resolution topology in differentiating closely related ASFV isolates, and drew new clues in the classification of some ASFV isolates. Genome-wide diversity of ASFV genomes was explored by pairwise sequence similarity comparison and ORF distribution comparison. Tandem repeat sequences were found widely distributed and highly varied in ASFV genomes. Structural variation and highly variable poly G or poly C tracts also contributed to the genome diversity. This study expanded our knowledge on the patterns of genetic diversity and evolution of ASFV, and provided valuable information for diagnosis improvement and vaccine development.