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#单细胞/空间组学

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Oct 15Thu
  1. Nature74

    Sexual dimorphism in epidermal stem cell dynamics.

    Intravital time-lapse imaging of lineage-labelled cells in mouse interfollicular epidermis supports a two-compartment model of epidermal homeostasis, with basal cells organized in a stem cell-transit-amplifying hierarchy. Female mice showed synchronized cell division, differentiation and delamination, linked to accelerated wound healing, while analyses of castrated mice showed male sex hormones promote stem cell differentiation and delamination. The work identifies sex-specific regulation of epidermal stem cell fate.

    Why it matters: It resolves a long-standing conflict over basal cell heterogeneity and reveals sex hormone control of epidermal stem cell fate.

  2. Nat Biotechnol69

    Mesenchymal thymic niche cells enable regeneration of the adult thymus and T cell immunity.

    A perivascular Postn+ mesenchymal subset of thymic stroma, identified by single-cell analysis of human and mouse tissue, proved to be a critical niche for T lymphopoiesis. Depleting these cells, which likely produce the chemokine Ccl19, blocks recruitment of T cell progenitors, and the subset declines with age and after hematopoietic stem cell transplant conditioning. Adoptively transferred Postn+ cells durably engraft the atrophic thymus, recruit early T progenitors, increase T cell neogenesis and improve T cell responses to vaccination; Ccl19-expressing mesenchymal populations give similar effects.

  3. biorxiv.org54

    Transcriptomic and phenotypic characterization of Alzheimer's disease risk genes in neurons and astrocytes highlights shared and cell type specific cellular mechanisms

    Knockouts of roughly 250 candidate Alzheimer's disease genes in iPSC-derived iNeurons and iAstrocytes show highly cell-type-specific effects that converge on shared pathways. Disease-linked expression programs from postmortem patient samples responded to the knockouts, and phenotypic analyses profiled each gene. The screen identified CCDC6 roles in cell cycle and activation state in iAstrocytes and C2orf49 regulation of endoplasmic reticulum stress responses in iNeurons.

  4. nature.com80

    Sexual dimorphism in epidermal stem cell dynamics

    Long-term intravital imaging of ear skin epidermis shows the interfollicular epidermis is not maintained by a single equipotent compartment: basal cells pass through an intermediate transit-amplifying-like state with limited proliferative potential before differentiating. Tracking labelled clones over 5 months, combined with single-cell expression profiling and biophysical modelling, reveals stochastic but locally coordinated stem cell renewal. Sister-cell events show temporal coordination strongly enriched in female mice, and functional experiments tie this to sex hormone regulation of basal cell dynamics.

    Why it matters: Revises the model of epidermal stem cell maintenance and shows sex hormones directly shape basal cell fate decisions.

Oct 14Wed
  1. biorxiv.org40

    Early-onset spontaneous murine mammary tumors show increased lymphocyte representation and reduced MHC antigen presentation

    A wild-derived PWK/PhJ genetic background accelerates HER2/neu-driven mammary tumor onset and reshapes the tumor immune microenvironment. (BALBxPWK) F1 NeuT females developed tumors at 10 weeks versus 15 weeks in BALB NeuT mice (p < 0.0001), with more tumor-infiltrating T and B cells but lower expression of cytotoxicity genes Tox, Ltk, Nkg7, and Gzmb. Proteomics found coordinate down-regulation of Stat1, Tapbp, Parp9, and Dtx3l with MHC class I and II proteins, indicating that inherited background, not the oncogene alone, governs antigen presentation and immune recognition in these tumors.

  2. biorxiv.org45

    A multimodal precision oncology platform integrating genomics,single-cell transcriptomics, and functional drug screening expandstherapeutic options in pediatric brain tumors

    A tiered precision oncology framework combining deep whole-genome sequencing, single-cell RNA sequencing, and ex vivo functional drug screening was applied to 17 children with malignant CNS tumors. Functional screening gave every patient at least one high-confidence targeted-therapy or chemotherapy nomination, single-cell RNA sequencing found an average of 37 druggable gene targets per patient, and high-confidence targeted-therapy recommendations rose fourfold. Functional classifications matched outcomes in 8 of 10 evaluable cases.

  3. biorxiv.org45

    Cyclic Hypoxia drives Wnt5a-ROR1 stroma-tumor crosstalk promoting breast cancer growth

    Cyclic hypoxia, unlike stable hypoxia, reprograms the triple-negative breast cancer microenvironment in a cell type specific way: it reverses chronic hypoxia-induced cell cycle arrest and a stabilized WNT5A+/COL6+ mesenchymal subpopulation, activates fibroblasts, and suppresses MSC proliferation. Single cell RNA and ATAC sequencing of a multicellular TNBC co-culture traced the effect to paracrine WNT5A/B-ROR1 signaling between fibroblasts and cancer cells. Blocking this crosstalk in a mouse CAF-TNBC co-xenograft model reduced tumor growth in vivo.

  4. biorxiv.org41

    Spatial transcriptomics reveals interferon pathway enrichment in early relapsing serous carcinoma

    Spatial transcriptomics of matched treatment-naive adnexal and omental tumors from nine high-grade serous carcinoma patients found that short platinum-free interval tumors show an interferon-driven inflammatory phenotype at both sites. C3, IFI27 and BST2 were consistently associated with short PFI across sites and validated by RNA in-situ hybridization; in two public ovarian cancer cohorts, high C3 expression was significantly associated with shorter platinum-free survival. The work nominates C3 as a candidate prognostic biomarker and potential therapeutic target.

  5. medrxiv.org52

    Beyond ERBB2 amplification: RNA and proteomic HER2 assessment for pan-tumor treatment stratification

    RNA-based and proteomic HER2 screening identified HER2-enriched tumors beyond ERBB2 amplification in a pan-tumor cohort of 1,331 biopsies, with validation in 3,898 external biopsies. All six objective responses among 51 treated patients occurred in tumors positive by ERBB2 mRNA and the combined RNA-signature. ERBB2 mRNA positivity was linked to longer time on treatment (hazard ratio 0.42) and overall survival (0.41), supporting prospective evaluation for treatment selection.

Oct 13Tue
  1. biorxiv.org51

    Spatial context of cellular heterogeneity in triple-negative breast cancer reveals actionable subtypes

    Bulk and spatial transcriptomics with cellular mapping of breast tissue from a large patient cohort identified three reproducible TNBC ecosystem subtypes with distinct spatial tumor-microenvironment architectures and treatment-response phenotypes: an immune-exhausted subtype associated with immune checkpoint therapy, a fibrotic/hypoxic subtype, and a metabolically reprogrammed subtype driven by nuclear-receptor and fatty-acid signaling. Multiplexed imaging independently confirmed the immune-infiltrated versus stromal-excluded architectures, and subtype-specific markers offer a basis for subtyping and candidate therapeutic vulnerabilities.

  2. biorxiv.org49

    Spatially resolved tumor-microenvironment architecture defines therapeutic response in unresectable hepatoblastoma

    Spatially organized tumor-microenvironment architecture distinguishes clinical outcomes in unresectable hepatoblastoma. Spatial transcriptomics (10x Visium, n = 11 tumors) and single-cell spatial imaging (NanoString CosMx, n = 3 tumors) on post-chemotherapy explants identified three architectures: relapse-prone tumors showed centralized, TME-dominated organization with SPP1+ TAMs, CAFs, hypoxia and MDK-LRP1 signaling, while non-relapse tumors showed compartmentalized tumor-immune interactions and preserved epithelial differentiation. Spatial architecture, not composition alone, may explain variable response beyond current risk stratification.

  3. nature.com52

    Clonal heterogeneity in human pancreatic ductal adenocarcinoma and its impact on tumor progression

    Single-cell RNA sequencing and spatial transcriptomics were applied to pancreatic ductal adenocarcinoma tumors to characterize tumor heterogeneity and clonal evolution. The work maps how clonal subpopulations are distributed within tumors and how that heterogeneity bears on tumor progression. The dataset also serves as a resource for future research on this cancer.

Oct 11Sun
  1. biorxiv.org56

    A Unified Comparison of 10X Genomics and Parse Biosciences scRNA-seq Technologies

    Single-cell RNA-seq data from 10X Genomics Chromium and Parse Biosciences Evercode WT are not directly interchangeable, according to a comparison of seven matched sample pairs from five studies. Platform-level differences were substantially larger than biases from Parse priming chemistry, which introduced a GC-content bias, and Parse showed a compositional shift consistent with relative enrichment of nuclear RNA. Background RNA contamination in Parse was comparable in magnitude to that in 10X, contrary to claims of substantially lower contamination.

  2. biorxiv.org52

    Transcriptional perturbation effects remain structured beyond the leading global trend

    Gene perturbations contribute unevenly to the known leading global transcriptional trend, and substantial structure persists beyond it, including perturbation-specific effects that transfer across datasets and a common hierarchy of responsive genes shared across perturbations. These patterns let simple prediction strategies stay competitive even for effects beyond the leading global component.

  3. biorxiv.org62

    Spatiotemporal AI modeling of gene regulation and variant effects in the developing human brain

    Seal, an interpretable AI transfer learning framework, models gene expression and variant effects with spatiotemporal resolution across 26 brain regions, 30 cell types, and seven developmental stages of the human brain. Applied to GWAS, it identifies cell types and developmental windows relevant to six neuropsychiatric conditions, and in Simons Simplex Collection autism whole genome data it uncovers a significant burden of de novo regulatory variants in transient fetal excitatory neurons.

    Why it matters: It links disease-associated variants to specific cell types and developmental windows in the developing brain.

  4. biorxiv.org68

    Disrupted chromatin architecture blocks B lymphopoiesis in Down syndrome

    Three-dimensional genome architecture organizes human fetal haematopoiesis and explains the B-lineage defect in Down syndrome. Using ChromE-seq, a new single-cell assay jointly profiling chromatin conformation and transcription, the authors built a multimodal atlas of ~400,000 haematopoietic cells from disomic and trisomy 21 fetal liver. Trisomy 21 disproportionately disrupted B-lineage architecture, weakened an EBF1-centred regulatory circuit, and deleting a T21-sensitive EBF1 loop anchor reproduced the CLP-to-B-progenitor bottleneck seen in T21.

    Why it matters: Links 3D chromatin architecture to lineage priming and identifies an EBF1 circuit behind the trisomy 21 B-cell defect.

  5. biorxiv.org69

    Scalable methylome-transcriptome profiling resolves clonal organization in human hematopoiesis

    Droplet-MT jointly profiles transcriptomes and methylomes at ~10,000 cells per library, using methylation epimutations for mutation-independent clonal reconstruction and label transfer at ~0.2% CpG coverage to cut sequencing cost. Applied to ~21,000 paired profiles from healthy blood and longitudinal acute myeloid leukemia, it resolved small and expanded clones with heterogeneous lineage output and distinguished malignant clonal abundance changes, state remodeling within persistent clones, and recovery of healthy polyclonal hematopoiesis. Malignant monocytes stayed transcriptionally and epigenetically distinct from healthy and recovery-associated cells despite treatment-associated remodeling.

    Why it matters: It offers a scalable way to link clonal ancestry to molecular state in human hematopoiesis and leukemia.

  6. Sci Adv77

    Extracellular matrix-targeted TNC-scFv armoring enhances CAR T cell persistence and antitumor activity in solid tumors.

    Armoring CAR T cells with a secreted tenascin-C-targeted single-chain variable fragment (TNC-scFv) enhanced cytotoxicity, persistence, and reduced exhaustion in vitro and in xenograft tumor models. Single-cell transcriptomics showed the approach reprograms the tumor microenvironment toward a CD8+ T cell-enriched, functionally active immune landscape, and humanized tumor models showed robust antitumor responses with minimal systemic toxicity. Combining the armoring with interleukin-2 further increased efficacy while mitigating cytokine-associated toxicity, establishing extracellular matrix-directed armoring as a generalizable strategy for solid tumors.

    Why it matters: It offers a generalizable armoring strategy that improves CAR T cell function against solid tumors, where efficacy has been limited.

Oct 10Sat
  1. Nature80

    Dynamics of human cardiogenesis and its disruption in trisomy 21.

    A spatially resolved single-cell multiomics map of the developing human heart defines 21 tissue niches, resolves three pacemaker cell subtypes in the sinoatrial node, and traces maturation trajectories of atrial and ventricular cardiomyocytes. Trisomy 21 hearts show depletion of compact cardiomyocytes and increased apoptosis relative to euploid hearts, a finding validated in isogenic-matched induced pluripotent stem cell-derived cardiomyocytes, providing a mechanistic lead on congenital heart disease risk in Down's syndrome.

    Why it matters: It links a cellular deficit in trisomy 21 hearts to congenital heart disease risk using a spatial human cardiac development atlas.

  2. doi.org49

    JAK-inhibitor treatment induces rapid yet incomplete immune reconstitution in STAT1 gain-of-function

    JAK inhibitors produced rapid but incomplete immune reconstitution in two STAT1 gain-of-function patients carrying p.R321S and p.T385M mutations. Changes were seen as early as 1 week after treatment: T cells rebalanced toward a homeostatic status, TCR repertoire diversity increased quickly, and transcriptional dysregulation in monocytes improved, though defects such as natural killer deficiency persisted in one patient. The work defines both the therapeutic reach and the limits of JAK inhibition in STAT1 GOF.

  3. Cell83

    A fluctuation test for gastruloid heterogeneity.

    Organoid heterogeneity traces partly to heritable differences in founder stem cells, not just culture conditions. Monoclonal gastruloids grown from single mouse embryonic stem cells showed extensive variability in development, mesodermal versus neural bias, and atypical cell types. DNA Typewriter lineage recording showed that fate biases arise before gastruloid induction, with more closely related founders producing more phenotypically similar gastruloids, and that fate-predictive differences map to gene expression, chromatin accessibility and imprinted loci.

    Why it matters: It locates a cell-intrinsic, heritable source of organoid heterogeneity and provides a lineage recorder to track it.

Oct 9Fri
  1. biorxiv.org48

    Paired single-nucleus and spatial transcriptomics of the lung adenocarcinoma invasion sequence reveal niche domains and candidate reversal compounds

    A single-nucleus and spatial transcriptomic atlas of the lung adenocarcinoma invasion sequence (413,697 nuclei, 23 patients; 56 Visium sections, 25 patients) resolves 39 cell subtypes and seven niche-domain archetypes, only one restricted to invasive disease. After controlling for sequencing depth, the invasive domain retains an ECM/interstitial identity, with the fibroblast ECM programme higher in invasive disease in 20 of 22 paired cases (P=0.0033). Querying LINCS returned 34 candidate reversal compounds, dominated by PI3K/mTOR inhibitors, though several other analyses yielded negative results.

  2. biorxiv.org58

    High-throughput identification of chromatin-opening transcription factors

    Pooled CRISPR activation of endogenous transcription factors in mouse embryonic stem cells reveals which TFs can open chromatin when newly expressed. After screening guides targeting 240 developmental TFs, the authors profiled gene expression and chromatin accessibility in ~140,000 single cells for 60 TFs. Some, like Cdx2 and Sox10, open distal sites on their own, while others require co-TFs through preexisting heterogeneity or hierarchical activation, such as Sox7 inducing Gata6.

  3. Cancer Cell67

    Spatial omics resolves adrenergic and mesenchymal cell states in neuroblastoma.

    Established cell line-derived signatures fail to identify mesenchymal (MES) neuroblastoma cells in patient tumors, so new ADRN/MES signatures were built from early-passage orthotopic patient-derived xenografts. Applied to 54 neuroblastoma tumors analyzed by sc/snRNA-seq, bulk RNA sequencing, spatial transcriptomics and spatial proteomics, the signatures identify MES tumor cells and show that high MES gene expression correlates with worse event-free and overall survival.

  4. biorxiv.org49

    Multi-Omic and Spatial Profiling Defines Outcome-Associated Tumor States in Head and Neck Adenoid Cystic Carcinoma

    Poor survival in head and neck adenoid cystic carcinoma is marked by loss of myoepithelial tumor cells and expansion of MYC/E2F-driven, actively dividing luminal states, defined by integrating bulk, single-cell, and spatial transcriptomes from 25 HNACC tumors. Both outcome groups share a myoepithelial-like origin, so aggressiveness reflects position along a shared developmental path. A four-gene classifier capturing this state predicted survival in an independent cohort, outperforming larger signatures and flagging aggressive subgroups in two others, supporting prospective risk stratification and proliferative-directed therapy.

  5. biorxiv.org51

    Single-nucleus multi-omics reveals reversible molecular signatures in skeletal muscle of patients with heart failure with preserved ejection fraction

    Single-nucleus multiome profiling of 140 skeletal muscle biopsies from 95 individuals (25 healthy controls, 70 HFpEF patients) maps molecular signatures of skeletal muscle remodeling in HFpEF, including type 1 fiber and pericyte depletion and type 2x fiber enrichment. Paired biopsies from 45 HFpEF patients before and after a supervised diet and exercise intervention show the chromatin accessibility and transcriptional changes were partially reversible. HFpEF-linked chromatin was enriched for heart failure and cardiometabolic GWAS signals.

  6. biorxiv.org51

    Pdk1-dependent metabolic heterogeneity promotes aggressive colorectal cancer through cell-intrinsic interferon signaling

    Pdk1 expression marks metabolically distinct cancer cell populations in colorectal tumors, and Pdk1-high cells drive tumor growth, 5-fluorouracil chemoresistance and relapse in orthotopic CRC models. These cells show an EMT, stem cell-like phenotype with increased interferon signaling, triggered by mitochondrial DNA release into the cytosol after mitochondrial remodeling. Blocking IFN signaling impairs their tumorigenic and aggressive features, linking metabolic heterogeneity to cell-intrinsic IFN signaling in aggressive CRC.

  7. biorxiv.org52

    Tumour-stroma signaling drives a reversible program with neural-like features in cancer-associated fibroblasts

    A NES+SOX4+NOTCH1+ neural-associated program in pancreatic cancer-associated fibroblasts is reversible rather than a fixed identity. Spatial transcriptomics from normal pancreas to invasive carcinoma identified EGF, FGF2 and BDNF as candidate tumor-to-fibroblast signals; EGF and FGF2 induced the program in patient-derived CAFs and fibroblast cell lines, and withdrawal reversed it at protein and transcriptional levels. MAPK/ERK signaling and ETS-family transcription factors drive the state, which pan-cancer single-cell analysis found enriched in CAFs across multiple cancer types.

  8. biorxiv.org43

    Inhibitory Nectin-2/TIGIT interactions between CD163+ macrophages and CD8+ T cells in spatially defined immune niches associate with poor outcomes in neuroblastoma

    CD163+ macrophages emerge as the dominant immunosuppressive interaction partner of T cells in neuroblastoma, engaging the TIGIT/PVR/Nectin-2 axis mainly at the tumor edge and in immune cores. Imaging mass cytometry (n=14) and spectral flow cytometry (n=18) on samples from 28 patients revealed T cell-excluded tumor niches and dysfunctional, tissue-resident T cells, with macrophage CD163 and Nectin-2 expression correlating with poor survival. The findings support combining strategies that boost T cell infiltration with blockade of inhibitory signaling.

Oct 7Wed
  1. nature.com56

    Dynamics of human cardiogenesis and its disruption in trisomy 21

    Single-cell and spatial multiomics were combined to map niches in the developing human heart, defining the organization of pacemaker cells and the processes of cardiomyocyte maturation and compaction. The same approach exposed developmental perturbations associated with trisomy 21, giving a cellular and spatial framework for how cardiogenesis proceeds and where it is disrupted.

  2. nature.com81

    Alveolar stem cells transdifferentiate to drive bronchiolar regeneration

    Alveolar type II (AT2) cells can cross anatomical boundaries and transdifferentiate into functional club and ciliated cells to repair injured bronchioles in vivo. Using a dual-gene-marker lineage tracing system that distinguishes AT2 cells from bronchoalveolar stem cells, the authors show that AT2-to-club conversion depends on integrin-β1-mediated migration and Notch-dependent fate specification, with infiltrating immune cells secreting SPP1 to direct AT2 migration toward injured bronchioles. The work provides definitive in vivo evidence of alveolar-to-bronchiolar repair, resolving ambiguity left by conventional Sftpc-creER tracing.

    Why it matters: It resolves whether alveolar cells repair bronchioles in vivo, with mechanistic detail relevant to airway regeneration therapies.

  3. nature.com53

    Genome accessibility reveals disease risk that gene expression misses

    Most disease-associated genetic variants act not on genes directly but on genome accessibility that changes gene expression. Simultaneous analysis of gene expression and accessibility in 10 million immune cells from 1,108 people now links disease-associated changes in accessibility to gene expression. The work gives a route to detecting disease risk that expression data alone misses.

  4. biorxiv.org45

    Dynamic Schlafen 11 (SLFN11) expression revealed by single-cell RNA sequencing of clonal human cancer cells

    SLFN11, a determinant of sensitivity to DNA-damaging therapies, is heterogeneously expressed among individual cells. Immunofluorescence microscopy and single-cell RNA sequencing across eight human cancer cell lines showed cell-to-cell heterogeneity at protein and RNA levels, with SLFN11 coexpressed with a stress-response state and genome maintenance programs and inversely correlated with protein translation pathways. Public single-cell RNA-sequencing datasets of human SCLC tumors confirmed the heterogeneous distribution, indicating dynamic single-cell regulation and a potential reservoir of intrinsic chemotherapy resistance.

  5. biorxiv.org47

    Analysis of Naturally Arising Simple Deletions in Single Human Colon Crypts with Age

    Simple deletions in single human colon crypts arise mainly through nonhomologous DNA end joining: of 4,264 deletions of two or more nucleotides, about 71% fit NHEJ and under 1.5% fit alternative end joining, while about 58% of all simple deletions are consistent with strand slippage. NHEJ-type simple deletions were roughly 8-fold more frequent than NHEJ-like complex indels, and both lesion classes accumulated about 10-fold across the lifespan from 0.8 months to 90 years in people without radiation or chemotherapy. Radiation treatment increased non-slippage deletions with little effect on slippage deletions.

Oct 6Tue
  1. biorxiv.org54

    RNA and protein are not interchangeable in single-cell spatial multi-omics

    Paired Xenium profiling of 21 matched RNA and protein targets across roughly 1.8 million cells from lung adenocarcinoma and metastatic castration-resistant prostate cancer shows the two modalities are not interchangeable. Lineage markers were concordant, but PD-1, PD-L1 and LAG-3 showed little agreement, and spatial organization was more discordant than overall abundance. The work sets rules for when spatial transcriptomics can proxy for protein and when orthogonal validation is needed.

  2. biorxiv.org47

    Conservation of gene co-expression networks and neuropsychiatric-neurological disease gene programs between mouse and human frontal cortex at single-cell resolution

    Co-expression partners of individual genes are only modestly conserved between mouse medial PFC and human dorsolateral PFC: across 13,214 genes and 246,211 single-nucleus RNA-seq profiles, the median partner similarity was 0.169, rising to at most 0.349 after noise correction. Co-expression modules, however, were strongly preserved, and four of five human modules recurred in an independent human dataset. Neuropsychiatric disease genes were no more conserved than matched control genes, and no disease gene showed different partners across species, temperating assumptions of gene-level conservation in mouse models.

  3. biorxiv.org50

    Matched primary-metastasis single-nucleus and spatial profiling of leiomyosarcoma identifies antigen-presenting fibroblasts at the tumor-organ interface

    Matched primary and metastatic leiomyosarcoma samples reveal organ-specific malignant programs, with a stress- and hypoxia-associated program in lung metastases and a proliferative, matrix-remodeling program in liver metastases. Antigen-presenting cancer-associated fibroblasts were enriched in metastases (p = 0.001) and formed a band at the tumor-organ interface, unlike their sparse random distribution in primaries. Spatial profiling of 21 patients further defined three histomolecular phenotypes, including a GPNMB phenotype potentially targetable by GPNMB-directed therapies.

  4. biorxiv.org40

    Spatial transcriptomics reveals tumour cell-intrinsic and microenvironmental features associated with survival in high-grade serous ovarian carcinoma

    Spatial transcriptomics of 122 treatment-naive high-grade serous ovarian carcinomas, using a 480-gene panel, identified 61 tumour-intrinsic genes nominally associated with overall survival, with five linked to longer and nine to shorter survival. 46 of these 61 associations were lost when expression was aggregated across all cells, showing that whole-tissue profiling obscures tumour-cell-specific survival signals. Multiple tumour-proximal immune populations predicted longer survival, while two fibroblast populations predicted shorter survival. The findings resolve the cellular origins of bulk survival signatures in HGSOC and link tumour-intrinsic expression to the surrounding microenvironment.

  5. biorxiv.org49

    Mechanistic Decoding of Pharmacodynamic Intratumoral Heterogeneity: A Pan-Cancer Regulatory Framework

    A pan-cancer analysis links single-cell transcriptomes from 1,279 samples across 24 cancer types with drug-response profiles for 1,218 compounds, defining 425 hub genes associated with predicted treatment-response heterogeneity. A multi-omics case study in lung adenocarcinoma identifies four regulatory classes of candidate associations, including 3 transcription factors, 41 genomic alterations, 5 ligand-receptor pairs and 8 splicing genes, converging on 6 core tumor-intrinsic pathways. An online platform enables state-resolved drug-response analysis and candidate-gene exploration.

Oct 5Mon
  1. Nature72

    Type 2 immune history trains lung macrophages for viral disease tolerance.

    Prior type 2 inflammation from Nippostrongylus brasiliensis infection made mice fully survive lethal H1N1 influenza challenge 4-6 weeks later, while all unconditioned controls died by days 5-6. Protection came through reduced immunopathology, increased efferocytosis and accelerated tissue repair rather than lower viral burden, and required nerve- and airway-associated macrophages (NAMs) bearing an IL-4-STAT6-PPARγ and ARG1 chromatin program. The work establishes local trained immunity in lung-resident macrophages as a mechanism of viral disease tolerance.

    Why it matters: Identifies a macrophage-based trained-immunity mechanism for disease tolerance that could be targeted in severe respiratory viral infections.

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