Genetic differences inferred from sequencing reads can be used for demultiplexing of pooled single-cell RNA-seq (scRNA-seq) data across multiple donors without WGS-based reference genotypes. However, such methods could not be directly applied to single-cell ATAC-seq (scATAC-seq) data owing to the lower read coverage for each variant compared to scRNA-seq. We propose a new software, scATAC-seq Variant-based EstimatioN for GEnotype ReSolving (scAVENGERS), which resolves this issue by calling more individual-specific germline variants and using an optimized mixture model for the scATAC-seq.
View Article and Find Full Text PDFClonal hematopoiesis of indeterminate potential (CHIP), a common aging-related process that predisposes individuals to various inflammatory responses, has been reported to be associated with COVID-19 severity. However, the immunological signature and the exact gene expression program by which the presence of CHIP exerts its clinical impact on COVID-19 remain to be elucidated. In this study, we generated a single-cell transcriptome landscape of severe COVID-19 according to the presence of CHIP using peripheral blood mononuclear cells.
View Article and Find Full Text PDFEndurance represents a highly adaptive function of fear memory and a major cause of maladaptive fear- and anxiety-related mental disorders. However, less is known about the mechanisms underlying the persistence of fear memory. The epigenetic gene regulation recently emerged as an important mechanism for memory persistence.
View Article and Find Full Text PDFSpermatogenesis is a complex process of sperm generation, including mitosis, meiosis, and spermiogenesis. During spermiogenesis, histones in post-meiotic spermatids are removed from chromatin and replaced by protamines. Although histone-to-protamine exchange is important for sperm nuclear condensation, the underlying regulatory mechanism is still poorly understood.
View Article and Find Full Text PDFAlthough most SARS-CoV-2-infected individuals experience mild coronavirus disease 2019 (COVID-19), some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1β-driven inflammatory response as compared to severe influenza.
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