Discover the 3D spatial transcriptomic atlas of cynomolgus monkey embryos at Carnegie stages 9 and 10 capturing key organogenesis steps! PMID:42098384, Nat Cell Biol 2026, @NatureCellBio https://doi.org/10.1038/s41556-026-01956-2 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪
Emerging evidence links gut microbiota dysbiosis to osteoarthritis by disrupting gut-barrier and hormonal functions. PMID:42098429, Nat Rev Rheumatol 2026, @NatRevRheumatol https://doi.org/10.1038/s41584-026-01378-2 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪
Shicheng Guo
Discover CLASHub: the game-changer with direct evidence of 1.3M miRNA-target interactions from CLASH data, leaving indirect databases behind. Get insights like never before! PMID:42098137, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-72902-x #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪
Discover TranscriptFormer: a groundbreaking model trained on 112M cells from 12 species across 1.53 billion years, classifying cells even over 685M years apart! PMID:42096520, Science 2026, @ScienceMagazine https://doi.org/10.1126/science.aec8514 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪
Reprogramming T cell-myeloid crosstalk boosts anti-PD-1 in 50% of advanced MMRd CRC, focusing on MHC+ C1Q+ CXCL9+. Key for overcoming immune… PMID:42092363, Cell Rep Med 2026 https://www.cell.com/cell-reports-medicine/fulltext/S266637912600203X?rss=yes&utm_source=dlvr.it&utm_medium=twitter #Medsky 🧪
Explore a groundbreaking machine-learning tool analyzing over 10 million spatial transcriptomes to profile tumor microenvironments, aiding in cancer treatment! PMID:42092150, Nature 2026, @Nature https://doi.org/10.1038/s41586-026-10452-4 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪
Study shows NaV clusters in membranes alter Na⁺ channel behavior. Single-channel methods overestimate Na⁺ current (INa) significantly, impacting predictions. PMID:42098094, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-72387-8 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪
Discover SCOTCH: a pipeline for single-cell RNA sequencing (lr-scRNA-Seq) with Nanopore, PacBio, 10X Genomics, and Parse. It models isoforms using sub-exons! PMID:42098110, Nat Commun 2026, @NatureComms https://doi.org/10.1038/s41467-026-72665-5 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪
The early organogenesis stage is a critical phase of embryogenesis that lays the foundation for organ development, and is characterized by dynamic and spatially organized transcriptional programs. However, limited spatial transcriptomic information has constrained our understanding of early primate organogenesis. Here we present a comprehensive three-dimensional (3D) spatial transcriptomic atlas of cynomolgus monkey embryos at Carnegie stages (CS) 9 and 10, capturing key morphogenetic events including cardiogenesis, gut tube regionalization, neurulation, axial mesendoderm patterning and early somitogenesis. Using high-resolution spatial transcriptomics and 3D reconstruction, we identify spatially defined lineage domains across germ layers and resolve regionally restricted gene expression, transcription factor activity, and signalling landscapes along major embryonic axes, exemplified by the emergence of dorsoventrally patterned spinal cord subpopulations during neurulation. Cross-speci
MicroRNAs (miRNAs) are short RNAs that regulate gene expression, critical for development and disease. Residing in Argonaute (AGO) proteins, miRNAs target messenger RNAs via complementary base-pairing. Current miRNA-target databases rely on indirect data from AGO crosslinking immunoprecipitation (AGO-CLIP). In contrast, CLASH (Crosslinking, Ligation, and Sequencing of Hybrids) employs proximity ligation within AGO complexes, providing direct miRNA-target interaction evidence. Existing CLASH datasets remain limited to a few human and mouse samples. Here, we present CLASHub, which integrates CLASH-defined interactions with gene and miRNA expression data from human, mouse, Drosophila, and C. elegans, spanning 25 cell types and tissues, including 91 new CLASH datasets generated from 17 cell types/tissues. The datasets also include samples with knockout of ZSWIM8, an essential component in target-directed miRNA degradation (TDMD), providing insights into miRNA turnover mechanisms. CLASHub f
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Osteoarthritis (OA) is a complex condition driven by biomechanical, metabolic and inflammatory factors; however, effective disease-modifying treatments remain unavailable. Growing evidence suggests that gut microbiota dysbiosis has an important role in OA pathogenesis, giving rise to the emerging concept of a functional and targetable gut–joint axis. Gut microbiota dysbiosis can impair enteroendocrine signalling, intestinal immunity and gut barrier integrity, alter the secretion of hormones and cytokines and facilitate the translocation of gut microorganisms, pro-inflammatory molecules and metabolites into the circulation or joints. These processes can disrupt systemic and local homeostasis, promote metabolic dysregulation and obesity, trigger low-grade inflammation and contribute to both the onset and progression of OA. Although these insights open up new avenues for disease-modifying treatments and build on the long-standing paradigm in OA, which primarily focuses on pain relief rath
Pancreatic ductal adenocarcinoma remains one of the deadliest malignancies, characterized by late diagnosis, aggressive biology and limited therapeutic success. Advances in multiagent chemotherapy have improved outcomes across disease stages, whereas precision medicine approaches are reshaping treatment paradigms. Personalized RNA vaccines and oncogenic KRAS-directed agents represent emerging immunological and molecular frontiers. Multimodal treatment regimens and surgical innovations, including vessel-oriented and minimally invasive techniques, have enhanced complete resection rates and enabled conversion of initially unresectable locally advanced pancreatic cancer into resectable disease. Increasingly, multidisciplinary, biology-guided strategies define resectability and the sequence of systemic and local therapies. The tumour microenvironment’s complex stromal and immune ecology remains central to therapeutic resistance but also offers opportunities for rational combination therapy.
Multicellular programs in the tumour microenvironment (TME) drive cancer pathogenesis and response to therapy but remain challenging to identify and profile clinically1–3. Here, we present a machine-learning framework for multi-analyte profiling of spatially dependent cell states and multicellular ecosystems, termed spatial ecotypes (SEs). By integrating over 10 million single-cell and spot-level spatial transcriptomes from diverse human carcinomas and melanomas, we identified nine SEs with broad conservation, each of which has unique biology, geospatial features and clinical outcome associations, including several linked to immunotherapy response. Notably, SEs were distinguishable by DNA methylation profiling and were recoverable from plasma cell-free DNA (cfDNA) using deep learning. In cfDNA from nearly 100 patients with melanoma, SE levels exhibited striking associations with immunotherapy response. Our data reveal fundamental units of TME organization and demonstrate a mu
Recent advances in long-read single-cell transcriptome sequencing (lr-scRNA-Seq) enable full-length isoform profiling at single-cell resolution. We present SCOTCH (Single-Cell Omics for Transcriptome CHaracterization), an end-to-end, platform-independent pipeline for isoform characterization from lr-scRNA-Seq data, supporting Nanopore and PacBio sequencing as well as 10X Genomics and Parse Biosciences protocols. SCOTCH models isoforms as combinations of non-overlapping sub-exons and applies dynamic thresholding for robust isoform assignment while efficiently address ambiguous mapping issues. By refining sub-exon boundaries through integration of read coverage with existing annotations and applying an iterative clustering strategy to reconstruct novel transcripts, SCOTCH reliably recovers more true novel isoforms than existing splice-graph-based methods, with poly(A)-aware filtering further reducing false-positive structures. Extensive simulations demonstrate improved quantification of
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Precise regulation of ion channel biophysics is an essential life process that governs electrical signaling in excitable tissues. Many ion channels, including voltage-gated Na+ channels (NaVs), exist in the membrane as clusters, which show distinct biophysical behavior not predicted by single-channel measurements. In both heterologous and native systems, we report that single-channel-based predictions significantly overestimated Na+ current (INa) amplitudes from multi-channel clusters. Computational modeling suggested that these observations could reflect interactions between adjacent channels, such as those recently reported between NaVs, and identified specific biophysical consequences thereof. This updated model not only accurately predicted behaviors observed from NaV clusters and consequent cellular physiology, but also suggested the possibility that clustered NaVs may respond differently to use-dependent pharmacological agents. Experiments validated the latter prediction and furt
Endosome maturation requires lumen acidification. Is progressive lumen acidification sensed by cytosolic-side molecules driving maturation? We show here that proton efflux through the endosomal Na⁺/H⁺ Exchanger (NHE6) activates the late endosome master regulator Rab7. Importantly, NHE6 is mutated in the childhood neurologic disorder Christianson Syndrome. We demonstrate that NHE6 interacts with the Rab7 GTPase-activating protein (GAP) TBC1D5 in a complex with Rab7 on the late endosome. This interaction and proton efflux are both required for Rab7 activation. TBC1D5 is potently inactivated with decreasing pH. A conserved histidine in the TBC1D5 GAP domain mediates pH-dependence. Furthermore, we show that neurons from mice engineered with a selective defect in NHE6 proton efflux exhibit blocked endosome maturation and disrupted Rab7 GTP-GDP cycling. In addition, knock-down of TBC1D5, thereby reducing Rab7 GAP activity, in NHE6 mutant neurons rescues Rab7 GTP-GDP cycling and endosome matu
