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HoxBlinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98-rearranged leukemia.
J Clin Invest
January 2025
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, United States of America.
Although nucleoporin 98 (NUP98) fusion oncogenes often drive aggressive pediatric leukemia by altering chromatin structure and expression of HOX genes, underlying mechanisms remain elusive. Here, we report that a Hoxb-associated lncRNA HoxBlinc was aberrantly activated in NUP98-PHF23 fusion-driven leukemias. HoxBlinc chromatin occupancies led to elevated MLL1 recruitment and aberrant homeotic topologically associated domains (TADs) that enhanced chromatin accessibilities and activated homeotic/hematopoietic oncogenes.
View Article and Find Full Text PDFAttention-aware differential learning for predicting peptide-MHC class I binding and T cell receptor recognition.
Brief Bioinform
November 2024
School of Computer Science, Northwestern Polytechnical University, Xi'an, 710129 Shaanxi, China.
The identification of neoantigens is crucial for advancing vaccines, diagnostics, and immunotherapies. Despite this importance, a fundamental question remains: how to model the presentation of neoantigens by major histocompatibility complex class I molecules and the recognition of the peptide-MHC-I (pMHC-I) complex by T cell receptors (TCRs). Accurate prediction of pMHC-I binding and TCR recognition remains a significant computational challenge in immunology due to intricate binding motifs and the long-tail distribution of known binding pairs in public databases.
View Article and Find Full Text PDFGraph contrastive learning of subcellular-resolution spatial transcriptomics improves cell type annotation and reveals critical molecular pathways.
Brief Bioinform
November 2024
School of Artificial Intelligence, Jilin University, Qianjin Street 2699, 130010 Changchun, China.
Imaging-based spatial transcriptomics (iST), such as MERFISH, CosMx SMI, and Xenium, quantify gene expression level across cells in space, but more importantly, they directly reveal the subcellular distribution of RNA transcripts at the single-molecule resolution. The subcellular localization of RNA molecules plays a crucial role in the compartmentalization-dependent regulation of genes within individual cells. Understanding the intracellular spatial distribution of RNA for a particular cell type thus not only improves the characterization of cell identity but also is of paramount importance in elucidating unique subcellular regulatory mechanisms specific to the cell type.
View Article and Find Full Text PDFHistopathology of the small airways: Similarities and differences between ageing and COPD.
Pulmonology
December 2025
Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester and Manchester University NHS Foundation Trust, Manchester, UK.
Age-related lung function decline is associated with small airway closure and gas trapping. The mechanisms which cause these changes are not fully understood. It has been suggested that COPD is caused by accelerated ageing.
View Article and Find Full Text PDFGlia control experience-dependent plasticity in an olfactory critical period.
Elife
January 2025
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, United States.
Sensory experience during developmental critical periods has lifelong consequences for circuit function and behavior, but the molecular and cellular mechanisms through which experience causes these changes are not well understood. The antennal lobe houses synapses between olfactory sensory neurons (OSNs) and downstream projection neurons (PNs) in stereotyped glomeruli. Many glomeruli exhibit structural plasticity in response to early-life odor exposure, indicating a general sensitivity of the fly olfactory circuitry to early sensory experience.
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