Skip to content

#单细胞/空间组学

Today 0 items
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. biorxiv.org40

    Beyond the gene: contextualizing novel isoforms through pathway analysis in long-read single-cell RNA sequencing

    A new computational framework, Centroid-based Isoform Pathway Inference (CIPI), assigns biological context to the thousands of novel isoforms and genes uncovered by long-read single-cell RNA sequencing. Instead of relying on host-gene annotation or known protein domains, CIPI builds expression-based neighborhoods of reference genes and combines them with GO, KEGG, or Reactome pathway analyses to infer pathway-level roles for individual isoforms. The result is a hypothesis-generating method for prioritizing novel isoforms across the isonome.

  3. biorxiv.org44

    Mitigating genotype-driven bias improves atlas-scale single-cell DNA methylome profiling

    Masking variant positions before DNA methylation quantification reduces genotype-driven bias in pooled single-cell bisulfite sequencing, where C-to-T variants are misread as conversion events. In a human blood nuclei sciMET dataset from 10 healthy individuals (25,674 nuclei), the approach reduced donor-associated confounding during clustering and fewer spurious differentially methylated regions within the same cell type, while improving batch mixing and preserving biological variation relative to uncorrected workflows.

  4. biorxiv.org48

    scIRES-seq reveals multimodal molecular heterogeneity in CTCs from small cell cervical cancer

    scIRES-seq, a new single-cell framework linking immunophenotype, genetic variation, DNA methylation and gene expression, was coupled to real-time imaging spectral flow cytometry and applied to circulating tumor cells from a patient with metastatic cervical small cell neuroendocrine carcinoma. Tumor-matched copy-number alterations and targeted somatic variants established CTC identity, and methylation profiles matched metastatic tissue. Genetic and methylation analyses identified two CTC subpopulations that transcriptomes alone did not distinguish, showing the value of multi-omics profiling of rare cells.

    Why it matters: It offers a working method to integrate identification and multi-omic characterization of rare circulating tumor cells.

  5. 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.

  6. Nat Biotechnol63

    Multimodal learning enables chat-based exploration of single-cell data.

    CellWhisperer links transcriptomes to text through a multimodal embedding trained by contrastive learning on 1 million RNA sequencing profiles with AI-curated descriptions, feeding a large language model that answers questions about cells and genes in natural-language chats. Benchmarked for zero-shot prediction of cell types and biological annotations, it supported discovery in a meta-analysis of human embryonic development and is integrated with the CELLxGENE browser for combined graphical and chat exploration of gene expression.

  7. 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.

  8. 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.org42

    cit_gsa: gene set analysis for scRNA-seq with covariate adjustment

    cit_gsa is a one-step self-contained gene set differential expression analysis method for single-cell RNA-seq that supports more than two conditions and covariate adjustment, unlike existing two-step approaches. Benchmarks show better performance than state-of-the-art methods in complex scenarios, and real-data analysis confirms that covariate adjustment improves biological interpretation.

  2. 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.

  3. 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.

  4. biorxiv.org40

    Dysregulation of epithelial differentiation architecture underlies field cancerization in head and neck cancer

    AnnZarro is a point-and-click browser viewer that displays cell-by-cell and gene-by-gene matrices such as kernels and correlations linked to an AnnData object's cells × genes data. It reads only the matrix rows and columns each panel displays from zarr stores, so users can explore matrices larger than memory: on a laptop, a 100,000-cell part of Tahoe-100M opens in 4 s, and all 95.6 million cells draw in one plot in about 5 to 7 s. The tool lets experimental biologists explore data without code and computational biologists probe the relationships behind their analyses.

  5. 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.

  6. 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.

  7. 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. Nat Biotechnol40

    Ten years, tens of millions of cells.

    The Human Cell Atlas consortium, launched in October 2016 by around 100 researchers led by Aviv Regev and Sarah Teichmann to map the body's roughly 30 trillion cells, has grown into one of the largest collaborative efforts in biology. By 2024 it had released four integrated v1 atlases, including a Human Lung Cell Atlas with over 2 million cells from 486 individuals across 49 datasets. Its next stage, cataloguing billions of cells, will draw on spatial biology and AI advances.

  2. 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.

  3. 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.

  4. biorxiv.org53

    Benchmarked sequencing methods reveal hidden mosaic variation in the human brain

    Benchmarking four duplex sequencing methods against bulk and single-neuron genome sequencing in matched human brain tissue showed that mosaic variant recovery is strongly method-dependent, with limited caller-level concordance. The new RIVER tool integrates read-level evidence, expanding cross-method-supported candidates by roughly two orders of magnitude; orthogonal sequencing at ~10,000x validated about half of tested RIVER-rescued candidates. Recovered variants resolved broadly distributed and regionally restricted clones and traced lineage among individual neurons.

    Why it matters: A benchmarked method that expands usable mosaic variant markers changes how brain lineage and mosaicism can be studied.

  5. 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.

  6. biorxiv.org52

    A reference-calibrated spatial-statistical framework for quantifying stroma-tumor cell spatial associations from histology and its geometric limits

    A framework combining four spatial statistics with specimen-specific reference states recovers the presence, range, and strength of spatial associations directly from segmented histology, without requiring interaction models specified a priori. In controlled in silico tissues, tissue stromal architecture imposed geometric limits on recoverable interaction ranges, with event fraction constraining statistical sensitivity. Applied to an ALK+ NSCLC model during tyrosine kinase inhibitor therapy, it identified a strong stroma-associated proliferation bias of proliferating tumor cells relative to CAF-rich stroma extending approximately 30-60 micrometers.

    Why it matters: It shows spatial statistics in histology must be interpreted relative to tissue-specific reference states and gives measurable interaction ranges in tumors.

  7. nature.com51

    Live-cell imaging goes WHOLISTIC

    WHOLISTIC is a live-imaging platform that records cellular activity across the entire vertebrate body at single-cell resolution, using genetically encoded calcium sensors, high-speed volumetric fluorescence imaging, computational motion correction and tissue-scale activity analysis. Ruetten and colleagues built transgenic zebrafish expressing a calcium indicator in nearly all cell types and demonstrated the approach in adult Danionella cerebrum, with whole-body expansion microscopy supporting molecular and anatomical characterization of cell populations.

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. Cell76

    Mapping transcriptional responses to cellular perturbations with RNA fingerprinting.

    RNA fingerprinting maps transcriptional responses from new single-cell experiments onto reference perturbation dictionaries, assigning query cells probabilistically to one or more candidate perturbations. Benchmarks on ground-truth datasets show accurate single-cell assignments, scalability to genome-wide screens, and resolution of combinatorial perturbations. Applications include identifying p53 regulators under ribosomal stress, dose-dependent drug mechanisms of action, and cytokine-driven B cell heterogeneity in secondary influenza infection in vivo.

    Why it matters: It provides a framework for causal interpretation of single-cell data by matching cellular states to perturbations.

  2. 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.

  3. 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.

  4. 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.org66

    Random mtDNA mutagenesis maps genotype-phenotype associations across metabolic contexts and lineages

    mtDIVE, a random C→T mutagenesis platform, enables pooled mitochondrial forward genetics in human epithelial cells and zebrafish embryos, generating molecules from single substitutions to more than 100 mutations. Selection on mutant genomes and their transcriptional consequences depend on metabolic state and developmental lineage: obligate OXPHOS eliminates highly mutated cells by apoptosis, while glycolytic conditions promote their competitive displacement. Individual loci have modest, non-redundant effects that predict cell state beyond mutation burden, and cancer-recurrent variants are enriched among mutations linked to reduced mitochondrial transcription.

    Why it matters: It replaces one-allele-at-a-time mtDNA models with pooled forward genetics separating mutation identity from load.

  2. biorxiv.org53

    GRASS-MIL: graph-based representation and discovery of phenotype-associated spatial structures with multiple instance learning

    GRASS-MIL, a graph multiple-instance learning framework, predicts phenotypes from spatial single-cell data across incompatible platforms harmonized only by a shared cell-type vocabulary, and decomposes each sample-level prediction exactly into signed neighborhood contributions. Trained jointly on CosMx, Xenium and MERFISH data, it predicted treatment status in high-grade serous ovarian carcinoma with AUROC 0.74 and identified relapse-associated niches in non-small-cell lung cancer (AUROC 0.57). In lung adenocarcinoma it predicted 3-year mortality (AUROC 0.62) via a lymphoid-myeloid polarity. In simulations it separated phenotypes with identical cell-type composition but different spatial organization, where composition-based classifiers performed at chance.

  3. 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.

  4. 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.

  5. biorxiv.org55

    scPRIME-seq uncovers synchronized multimodal molecular collapse facilitated by pre-neoplastic epigenetic burden in prostate cancer

    scPRIME-seq, a high-throughput platform for simultaneous single-cell profiling of transcriptome, genome and DNA methylome, was applied to 436,908 cells from 29 prostate cancers and 15 benign tissues, resolving 30 cell types along a unified tumorigenic trajectory. The analysis located a tipping point where aneuploidy onset is temporally coupled with global methylomic alterations and transcriptomic rewiring. Early focal epigenetic alterations, including TMEM106A promoter hypermethylation, were present in founder aneuploid clones and benign tissues, pointing to a pre-neoplastic origin of the epigenetic burden and a tumor-permissive microenvironment.

  6. biorxiv.org60

    STEER-seq: a recombinase based platform for pooled multimodal single-cell perturbation screening

    STEER-seq is a virus-free platform for pooled ORF gain-of-function screening in human induced pluripotent stem cells, using Bxb1-mediated integration at a defined safe-harbour locus so each perturbation is expressed from a single copy in a common genomic context. Joint RNA and chromatin accessibility profiling linked transcription factor responses to chromatin remodelling. In a haematopoietic screen, SPI1 alone drove differentiation to HSC/MPP-like progenitors without exogenous cytokines, and scaling to around 2,000 human coding sequences uncovered factors inducing neural progenitor-, melanocyte- and vascular smooth muscle-like states.

    Why it matters: It removes random viral integration as a confound in pooled gain-of-function screens and works in hiPSCs at ~2,000-ORF scale.

  7. Cell78

    Comprehensive lineage tracing maps the landscape of cell fate decisions in mouse embryogenesis.

    PEtracer, a method that continuously installs heritable genetic marks, reconstructed lineage trees resolving ~75% of cell divisions across >1.4 million cells from 16 replicate mouse embryos, paired with deep transcriptional profiling. The resulting quantitative reference shows reproducible lineage architecture between replicate embryos and maps fate biases, restriction timing, progenitor pool sizes and lineage relationships, including progressive neural crest restriction and distinct mesodermal origins of endothelium. It replaces piecemeal fate maps with a whole-embryo, cell-level lineage reference for mammalian development.

    Why it matters: It delivers the first whole-embryo quantitative cell fate map with million-cell resolution across replicate mouse embryos.

  8. 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.

CBACBA Frontier Insights (CFI)Chinese Biopharmaceutical Association (CBA)www.cba-usa.org