CRISPR dependency screens in primary hematopoietic stem cells identify KDM3B as a genotype-specific vulnerability in IDH2- and TET2-mutant cells

CRISPR-Dependent Screening in Primary Hematopoietic Stem Cells Identifies KDM3B as Specific Susceptibility for IDH2 and TET2 Mutant Genotypes Background and Significance Clonal Hematopoiesis (CH) refers to the abnormal growth of genetically distinct subclones of cells initiated by specific mutations in Hematopoietic Stem Cells (HSCs). This phenomen...

Targeting Acute Myeloid Leukemia Stem Cells Through Perturbation of Mitochondrial Calcium

Targeting Acute Myeloid Leukemia Stem Cells Through Perturbation of Mitochondrial Calcium

This is an academic paper report on the study of acute myeloid leukemia (AML) stem cells. The study found that venetoclax treatment targeting the BCL-2 protein induces different mitochondrial calcium signaling changes in drug-sensitive and drug-resistant AML stem cells, thereby affecting their oxidative phosphorylation metabolism and survival. The ...

Mechanisms of Response and Tolerance to Active RAS Inhibition in KRAS-Mutant NSCLC

Response and Resistance Mechanisms of RAS Inhibitors in KRAS-Mutant NSCLC Research Background With the clinical development of RAS inhibitors, the treatment of KRAS-mutant Non-Small Cell Lung Cancer (NSCLC) faces a new turning point. However, in clinical practice, patients show poor long-term responses to RAS inhibitors, influencing clinical effica...

High-Throughput Discovery of MHC Class I- and II-Restricted T Cell Epitopes Using Synthetic Cellular Circuits

High-Throughput Discovery of MHC Class I and II Restricted T Cell Epitopes Using a Novel Synthetic Cellular Circuit Research Background and Issues In recent years, antigen discovery technologies have made remarkable progress, especially in the application of human T-cell receptors (TCRs) in the recognition of major histocompatibility complex (MHC) ...

Principled distillation of UK Biobank phenotype data reveals underlying structure in human variation

In this report, we present a detailed evaluation of a research paper published in the journal Nature Human Behaviour, titled “Principled Refinement of UK Biobank Phenotypic Data Reveals the Latent Structure of Human Variation.” The study, conducted by Caitlin E. Carey, Rebecca Shafee, Robbee Wedow, among others, was published online on XX XX, XXXX....

Mapping Medically Relevant RNA Isoform Diversity in the Aged Human Frontal Cortex with Deep Long-Read RNA-Seq

Academic Background RNA isoforms play a critical role in gene expression regulation. On average, human protein-coding genes contain over eight RNA isoforms, leading to nearly four distinct protein-coding sequences. Traditional short-read sequencing technologies, due to their limitations in read length, cannot accurately assemble and quantify RNA is...

Tracking-seq Reveals the Heterogeneity of Off-target Effects in CRISPR-Cas9-mediated Genome Editing

Transcriptomics Technology Tracking-Seq Reveals Off-Target Effect Heterogeneity Mediated by CRISPR-Cas9 Research Background With the rapid development of genome editing technologies, the CRISPR-Cas9 system has been widely used in biomedical research due to its high efficiency and ease of operation. However, a significant issue with the CRISPR-Cas9 ...

The Role of the IL-1β-Stat5 Axis in Autoimmune Neuroinflammation and Potential Therapeutic Strategies

Major Breakthrough in Research for Autoimmune Neuroinflammation Treatment Background Introduction Steroid resistance is a significant challenge in the treatment of many inflammatory diseases, particularly autoimmune neuroinflammation. In these diseases, TH17 cells (T helper 17 cells) are widely regarded as key contributors to steroid resistance; ho...

Targeted depletion of PD-1–expressing cells induces immune tolerance through peripheral clonal deletion

Inducing Immune Tolerance through Peripheral Clonal Deletion Targeting PD-1 Expressing Cells Background Introduction The establishment of T-cell receptor (TCR) repertoire through thymic negative selection is a key process for achieving self-tolerance and acquired tolerance post-organ transplantation. However, it remains unclear whether the specific...

G Protein–Coupled Receptor Endocytosis Generates Spatiotemporal Bias in β-Arrestin Signaling

Academic News Report: The Temporal and Spatial Bias in β-arrestin Signal Transduction Mediated by G Protein-Coupled Receptor Endocytosis Research Background Among cell surface receptor families, G protein-coupled receptors (GPCRs) constitute the largest family. Upon activation by ligands, they interact with various signaling proteins to trigger int...