A rapid chemical reprogramming system to generate human pluripotent stem cells.

Chemical reprogramming enables the generation of human pluripotent stem (hCiPS) cells from somatic cells using small molecules, providing a promising strategy for regenerative medicine. However, the current method is time consuming, and some cell lines from different donors are resistant to chemical induction, limiting the utility of this approach. Here, we developed a fast reprogramming system capable of generating hCiPS cells in as few as 10 days.

Single-cell RNA sequencing reveals cell type-specific immune regulation associated with human neuromyelitis optica spectrum disorder.

Introduction: One rare type of autoimmune disease is called neuromyelitis optica spectrum disorder (NMOSD) and the peripheral immune characteristics of NMOSD remain unclear.

Methods: Here, single-cell RNA sequencing (scRNA-seq) is used to characterize peripheral blood mononuclear cells from individuals with NMOSD.

Results: The differentiation and activation of lymphocytes, expansion of myeloid cells, and an excessive inflammatory response in innate immunity are observed.

All-potassium channel CRISPR screening reveals a lysine-specific pathway of insulin secretion.

Objective: Genome-scale CRISPR-Cas9 knockout coupled with single-cell RNA sequencing (scRNA-seq) has been used to identify function-related genes. However, this method may knock out too many genes, leading to low efficiency in finding genes of interest. Insulin secretion is controlled by several electrophysiological events, including fluxes of K depolarization and K repolarization.

Using graph-based model to identify cell specific synthetic lethal effects.

Synthetic lethal (SL) pairs are pairs of genes whose simultaneous loss-of-function results in cell death, while a damaging mutation of either gene alone does not affect the cell's survival. This makes SL pairs attractive targets for precision cancer therapies, as targeting the unimpaired gene of the SL pair can selectively kill cancer cells that already harbor the impaired gene. Limited by the difficulty of finding true SL pairs, especially on specific cell types, current computational approaches provide only limited insights because of overlooking the crucial aspects of cellular context dependency and mechanistic understanding of SL pairs.

Single-cell transcriptomics reveals cell type-specific immune regulation associated with anti-NMDA receptor encephalitis in humans.

Introduction: Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a rare autoimmune disease, and the peripheral immune characteristics associated with anti-NMDARE antibodies remain unclear.

Methods: Herein, we characterized peripheral blood mononuclear cells from patients with anti-NMDARE and healthy individuals by single-cell RNA sequencing (scRNA-seq).

Results: The transcriptional profiles of 129,217 cells were assessed, and 21 major cell clusters were identified.

Single-cell RNA sequencing reveals a pro-invasive cancer-associated fibroblast subgroup associated with poor clinical outcomes in patients with gastric cancer.

The protumor activities of cancer-associated fibroblasts (CAFs) suggest that they are potential therapeutic targets for the treatment of cancer. The mechanism of CAF heterogeneity in gastric cancer (GC) remains unclear and has slowed translational advances in targeting CAFs. Therefore, a comprehensive understanding of the classification, function, activation stage, and spatial distribution of the CAF subsets in GC is urgently needed.

Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms.

The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.

Single-cell heterogeneity analysis and CRISPR screens in MIN6 cell line reveal transcriptional regulators of insulin.

Diabetes mellitus is caused by either insulin resistance or insulin deficiency. The pancreatic β cells are the primary producers of insulin. Large-scale CRISPR screens combined with single-cell RNA sequencing (scRNA-seq) on β cells has identified novel insulin regulators and revealed the presence of a highly complex inner network.

The commensal consortium of the gut microbiome is associated with favorable responses to anti-programmed death protein 1 (PD-1) therapy in thoracic neoplasms.

Objective: Immune checkpoint inhibitors have revolutionized cancer therapy for multiple types of solid tumors, but as expected, a large percentage of patients do not show durable responses. Biomarkers that can predict clinical responses to immunotherapies at diagnosis are therefore urgently needed. Herein, we determined the associations between baseline gut commensal microbes and the clinical treatment efficiencies of patients with thoracic neoplasms during anti-programmed death protein 1 (PD-1) therapy.

Cytokines/Chemokines: Potential Biomarkers for Non-paraneoplastic Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common type of autoimmune encephalitis. This study focuses on finding new biomarkers to evaluate the clinical condition and provide new directions for treatment. A total of 44 cytokines/chemokines in the cerebrospinal fluid of 10 non-paraneoplastic patients and nine controls were measured.

SCSA: A Cell Type Annotation Tool for Single-Cell RNA-seq Data.

Currently most methods take manual strategies to annotate cell types after clustering the single-cell RNA sequencing (scRNA-seq) data. Such methods are labor-intensive and heavily rely on user expertise, which may lead to inconsistent results. We present SCSA, an automatic tool to annotate cell types from scRNA-seq data, based on a score annotation model combining differentially expressed genes (DEGs) and confidence levels of cell markers from both known and user-defined information.

A novel codon-based de Bruijn graph algorithm for gene construction from unassembled transcriptomes.

Most gene prediction methods detect coding sequences from transcriptome assemblies in the absence of closely related reference genomes. Such methods are of limited application due to high transcript fragmentation and extensive assembly errors, which may lead to redundant or false coding sequence predictions. We present inGAP-CDG, which can construct full-length and non-redundant coding sequences from unassembled transcriptomes by using a codon-based de Bruijn graph to simplify the assembly process and a machine learning-based approach to filter false positives.

Armet is an effector protein mediating aphid-plant interactions.

Aphid saliva is predicted to contain proteins that modulate plant defenses and facilitate feeding. Armet is a well-characterized bifunctional protein in mammalian systems. Here we report a new role of Armet, namely as an effector protein in the pea aphid, Acyrthosiphon pisum.