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#单细胞/空间组学

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Aug 29Sat
  1. Cell64

    Brain perivascular macrophages regulate endothelial cell function via a cMAF-dependent transcriptional program in mouse and human.

    The transcription factor cMAF controls brain perivascular macrophage identity and their IGF1-mediated communication with endothelial cells, and conditional cMAF deletion disrupts the macrophage phenotype and alters transcription in cerebral arteries. cMAF is also the main transcription factor for human perivascular macrophages. In Alzheimer's disease these cells upregulate cMAF and IGF1 to strengthen communication with vascular cells, a response lost in APOE4 carriers, and an uncharacterized cMAF polymorphism suggests the program is protective against AD.

    Why it matters: Links a macrophage transcription factor to endothelial function and Alzheimer's disease risk, with relevance to APOE4 carriers.

Aug 28Fri
  1. Nature73

    Aberrant excitatory neuronal ERBB4 promotes Alzheimer's disease pathology.

    Ectopic Erbb4 expression in excitatory neurons emerges as one of the earliest alterations in Alzheimer's disease mouse models, driving synapse loss, network abnormalities, gliosis, amyloid deposition and cognitive deficits. Deleting Erbb4 selectively in AD excitatory neurons abrogated these phenotypes, while overexpressing it in wild-type mice reproduced them without amyloid plaques, through mTOR signalling. Mediation analysis of human AD transcriptomic data links neuronal ERBB4 to tau propagation and cognitive decline.

    Why it matters: It identifies a neuronal receptor tyrosine kinase, ERBB4, as an early, mechanistic driver of AD pathology and a druggable target.

Aug 27Thu
  1. Science61

    A cross-organ single-cell analysis of hypertension.

    A single-cell analysis across six organs and tissues in angiotensin II-treated mice, Dahl salt-sensitive rats, and spontaneously hypertensive rats mapped gene programs tied to blood pressure and renal injury, including conserved vascular smooth muscle cell and renal tubular programs. Integration with human genomic data linked cell types to hypertension traits and prioritized a noncoding variant, rs28451064, whose genome-edited validation showed an in vivo effect on blood pressure and allele-specific regulation of local genes. The work delivers a multimodel, cross-organ cellular resource for hypertension research.

    Why it matters: Cross-organ single-cell mapping across three hypertension models with genome-edited validation of a blood pressure variant.

  2. Sci Adv52

    Maladaptive immune-fibrotic axis drives impaired long bone regeneration under mechanical instability.

    Controlled interfragmentary strain of 15 to 30% in a murine delayed-fracture model caused 3.3-fold more fibrotic tissue, delayed ossification and 1.6-fold lower callus stiffness compared with strain below 5%. Spatial transcriptomics tied high-strain calluses to fibrotic niches with Pdgfrb, Lgals3, Spp1 and Mmp9 signaling, and circulating CD206+ macrophages and CD25+ regulatory T cells predicted healing outcomes (R = 0.72). The work frames hypertrophic nonunion as dysregulated mechanical-immune crosstalk and provides a preclinical platform for testing it.

Aug 26Wed
  1. Cell62

    Multimodal brain cell atlas across the adult macaque lifespan.

    A single-cell atlas of transcriptomics and chromatin accessibility covers 2,955,873 nuclei from eight brain regions of 23 female cynomolgus macaques across the adult lifespan, including exceptionally old individuals. Age-related changes were cell-subtype- and region-specific, affecting synaptic communication and axon myelination, and multicellular networks in the pons and medulla emerged as a previously unrecognized hotspot of primate brain aging. Integration with human datasets defines transcription factors and chromatin remodeling programs linked to longevity and neurodegeneration.

    Why it matters: It locates a new hotspot of primate brain aging and links regulatory programs to longevity and neurodegeneration.

  2. Cell70

    Integrative spatial profiling of 3D genome organization and gene expression in tissue.

    Spatial Hi-C-RNA maps genome-wide chromatin contacts and transcriptomes from the same tissue section at near-single-cell resolution. Applied to mouse brain, developing embryos, and human melanoma, it tied A/B compartments, topologically associating domains, and loops to region- and cell-type-specific transcriptional programs, resolved chromatin and transcriptional remodeling during embryonic neuronal maturation, and identified melanoma intratumoral subdomains that RNA alone did not detect. It adds in situ 3D genome structure as a measurable layer of tissue biology.

    Why it matters: It adds genome-wide chromatin architecture, in situ and paired with RNA, as a new spatially resolved readout in tissue.

  3. Sci Adv48

    Hi-Cformer enables multiscale chromatin contact map modeling for single-cell Hi-C data analysis.

    Hi-Cformer, a transformer-based method, models multiscale blocks of single-cell chromatin contact maps through a specialized attention mechanism capturing dependencies across genomic regions and scales. It learns robust low-dimensional cell representations from sparse single-cell Hi-C data, improving cell type separation over existing methods, and accurately imputes interaction signals including topologically associating domain-like boundaries and A/B compartments. The learned embeddings also support accurate cell type annotation across intra- and inter-dataset scenarios.

  4. Nat Biotechnol69

    Simultaneous single-cell profiling of chromatin, transcriptome and surface markers with OneCell CUT&Tag captures epigenomic reprogramming.

    OneCell CUT&Tag delivers matched epigenome, full-transcriptome and surface marker profiles from every cell, with input as low as one cell and no need to aggregate cells computationally. Applied to mammary gland, it uncovered epigenomic priming of basal cells and showed that epigenomic and transcriptional remodeling are not fully synchronized during basal-to-luminal transdifferentiation. It also identified a role for H3K27me3 in shaping zygotic expression programs.

    Why it matters: Single-cell multiomics down to one-cell input makes rare-sample epigenome-plus-transcriptome profiling practical.

  5. Nature69

    Temporal uncoupling of radial glia lineage progression in cortical organoids.

    Radial glial progenitors in self-organizing cortical organoids, traced with MADM lineage mapping established in mouse embryonic stem cells, show high plasticity in proliferative potential rather than the strict temporal stereotyping seen in vivo. Clones in organoids display increased lineage restriction and reduced cortical projection neuron diversity despite uniform RGP transcriptional signatures and a single lineage trajectory. The work points to non-cell-autonomous cues, absent from self-organizing systems, as required for faithful temporal lineage control.

    Why it matters: It defines a specific defect of cortical organoids, lineage restriction, that limits their use as models of cortical development.

Aug 25Tue
  1. Cancer Cell73

    PD-1 blockade unleashes local hepatitis B virus-related B cell response inhibiting hepatocellular carcinoma.

    Anti-PD-1 efficacy in hepatocellular carcinoma can work through B cells, not only T cells. In a mechanistic study alongside a phase 2 trial of perioperative anti-PD-1 therapy in resectable recurrent HCC, late-recurrence patients showed two subtypes with T cell- or B cell-dominant tumor responses; B cell-dominant tumors had somatic hypermutation-driven antibodies against HBV core antigen within tumor tertiary lymphoid structures. In mice, HBcAg-reactive antibodies drove complement-mediated antitumor activity that enhanced anti-PD-1 response.

    Why it matters: It identifies a B cell and antibody mechanism inside tertiary lymphoid structures that underlies anti-PD-1 efficacy in HCC.

Aug 21Fri
  1. nature.com73

    Bonsai reconstructs tree representations for distortion-free visualization and exploration of high-dimensional data

    Bonsai, a Bayesian method with no tunable parameters, reconstructs single-cell omics data as maximum-likelihood tree structures, exploiting a 'blessing of dimensionality' so that high-dimensional distances are accurately represented along tree branches. Unlike t-SNE and UMAP, tests on real and simulated scRNA-seq data show it preserves pairwise distances between all cells at all scales and infers differentiation trajectories. Applied to cord-blood scRNA-seq, it recovers the known blood differentiation hierarchy and uncovers previously undescribed lineage relationships, with a webserver pipeline and interactive exploration app provided.

    Why it matters: Offers a parameter-free alternative to t-SNE and UMAP that preserves local and global structure in single-cell data without distortion.

  2. nature.com69

    Dysregulated adult hippocampal neurogenesis in major depressive disorders

    The largest multiomic atlas of the adult human hippocampus identifies disrupted neurogenesis, gene regulation and neural circuits in major depressive disorder. The atlas reveals molecular pathways and potential therapeutic targets related to stress, cellular aging and neuroplasticity. It changes the field's picture of adult hippocampal neurogenesis in depression from a hypothesis to a mapped, molecularly annotated process.

    Why it matters: It maps disrupted hippocampal neurogenesis and circuits in major depressive disorder at multiomic scale, pointing to therapeutic targets.

  3. Cancer Cell60

    Mapping cell type-resolved transcriptomic profiles to patient survival in pancreatic cancer.

    A prognostic atlas links cell type-resolved gene expression to overall survival in pancreatic ductal adenocarcinoma, integrating single-nucleus RNA-seq and longitudinal data from 152 patients and profiling 1.2 million cells, plus 3.1 million cells by spatial transcriptomics correlated with therapeutic response. The atlas identifies PLOD2, whose elevated expression predicts poorer outcomes across eight cell types, and a proof-of-concept degrader compound inhibits PDAC progression in vivo. The ctPANDA platform makes cell-type-level prognostic insights available to the research community.

    Why it matters: Moves prognostic transcriptomics from bulk-level to cell-type resolution and pairs the atlas with a candidate target and degrader.

Aug 20Thu
  1. Sci Adv60

    Geneformer-guided multiomics integration identifies Pbx1 as a network hub of hematopoietic stem cell aging.

    Aged hematopoietic stem cells carry two distinct transcriptional programs, one shared with megakaryocytes and one reflecting the most primitive HSC state, with developmental profiling indicating the primitive module rises prenatally and megakaryocytic priming emerges after birth. Using a fine-tuned Geneformer model, transcriptomic and epigenetic profiling, and transcription factor screens, the authors identified Pbx1 as a key regulator of these age-related changes, suppressing erythroid differentiation by repressing Gata1. The work nominates Pbx1 as a network hub and a target for modulating age-associated HSC dysfunction.

    Why it matters: It pins a mechanistic regulator, Pbx1, on age-linked shifts in HSC differentiation toward platelet production over erythropoiesis.

  2. Nat Med67

    Dysregulated adult hippocampal neurogenesis in major depressive disorders.

    Adult hippocampal neurogenesis appears stalled in nonmedicated individuals with major depressive disorder, according to integrated analyses of neurogenic trajectories, cell-type- and subfield-specific gene expression, chromatin accessibility and protein expression. The stalled process was linked to transcriptional regulation, stress-related reprogramming and interferon signaling, with excitatory and inhibitory neurons showing dysregulated transcription factor networks. The findings suggest pathogenetic overlap with autoimmune, neurodevelopmental and neurodegenerative diseases and point to therapeutic targets for hippocampus-dependent cognitive symptoms.

    Why it matters: It supplies human molecular evidence that neurogenesis is stalled in MDD and names mechanisms shared with other brain diseases.

Aug 19Wed
  1. Sci Adv56

    The extreme diversity of retinal amacrine cells has deep evolutionary roots.

    Integrating single-cell and single-nucleus transcriptomic atlases from 24 vertebrate species, this work identifies 42 orthologous amacrine cell types, most showing one-to-one correspondence across amniotes and often across vertebrates. Core molecular identities are conserved while abundance and gene expression vary, and amacrine cell diversity scales with retinal ganglion cell diversity, indicating coevolution. The authors propose amacrine cells arose from an amacrine cell-retinal ganglion cell hybrid precursor. This replaces a fragmented view with a unified evolutionary framework for an inhibitory neuron class.

  2. Nature81

    Antigen presentation by CD40+MHC-II+ astrocytes promotes CNS autoimmunity.

    Astrocytes expressing CD40 and MHC-II present antigen to CD4+ T cells and drive CNS autoimmunity. Direct astrocyte-CD4+ T cell interactions enhanced pathogenic Th17 responses in experimental autoimmune encephalomyelitis, and CD40 activation by T cell CD40L induced PLIN4-positive lipid droplets that supply acetyl-CoA for p65 acetylation-dependent NF-κB activation and antigen presentation. CD40+MHC-II+LD+ astrocytes were detected in multiple sclerosis samples by single-nucleus RNA sequencing and immunohistochemistry, defining a previously unrecognized mechanism of astrocyte-driven autoimmunity.

    Why it matters: It identifies astrocytes as antigen-presenting cells driving CNS autoimmunity, with evidence in mouse models and multiple sclerosis tissue.

Aug 18Tue
Aug 16Sun
  1. Science75

    Chemically induced skin tumors arise from long-lived stem cells of the upper hair follicle.

    Chemically induced skin tumors in mice arise predominantly from Lgr6+ and/or Lrig1+ stem cells of the upper hair follicle and only very rarely from Lgr5+ and Krt19+ bulge stem cells, based on fluorescent lineage tracing, single-cell transcriptomics, and duplex sequencing. Lgr6+ stem cells initiated by dimethylbenzanthracene expanded clonally after tumor promotion, carrying the canonical Hras Q61L mutation, while spontaneous Kras mutations expanded only when Hras was deleted, revealing competitive Hras-Kras interaction in clonal selection.

    Why it matters: It pins the cell of origin for chemically induced skin tumors and uncovers Hras-Kras competition shaping clonal selection.

Aug 14Fri
  1. Cell74

    An emergent disease-associated motor neuron state precedes cell death in ALS.

    A distinct cell state, named disease-associated motor neurons (DMs), emerges in vulnerable alpha motor neurons before death in the SOD1-G93A mouse model of ALS. Longitudinal single-nucleus transcriptomes, chromatin accessibility and spatial transcriptomics defined transcription factor networks governing the transition and subtype-selective vulnerability. Upregulation of DM-associated transcription factors in human motor neurons induced DM features, and the DM signature was conserved in human ALS spinal cord, with differentially accessible regions enriched for ALS risk variants.

    Why it matters: It defines a conserved, genetically linked motor neuron state that precedes degeneration in ALS.

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