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Results for “single-nucleus sequencing”

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PubMed2026

Multiancestry genome-wide association and multiomics analyses elucidate spatiocellular features of multiple sclerosis genetics.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by demyelination disseminated in space and time. Here we performed a genome-wide association study (GWAS) using 688 MS cases and 205,199 controls from the Japanese population and identified significant associations in the major histocompatibility complex region and a population-specific risk variant in 11q24. Through cross-population GWAS meta-analyses using a total of 29,374 cases and 1,843,563 controls from 4 ancestral populations, we identified 22 novel susceptibility loci. Integration of GWAS and single-cell and single-nucleus RNA sequencing of peripheral blood mononuclear cells and subcortical lesions from patients with MS revealed enrichment of genetic risk factors for MS in CD4+ T helper cell lineage and regulatory T cells, as well as in endothelial cells. Furthermore, spatial transcriptomics of subcortical lesions demonstrated spatial and temporal heterogeneity in associations with MS genetic risk. Our study demonstrates the value of investigation of spatiocellular features of disease genetics across diverse populations and omics modalities.

Humans↗

PubMed2026

Spatially guided in vivo single-cell functional genomics of postnatal heart.

Understanding how spatial organization and cell-cell interactions shape gene regulatory programs is central to decoding tissue development and function. The transition at birth, marked by increased circulatory demands and rapid tissue growth, requires precise spatiotemporal coordination of cardiac maturation. In this study, we generated a high-resolution spatial and temporal atlas of the postnatal mouse heart by integrating single-nucleus RNA sequencing with image-based spatial transcriptomics. This framework revealed dynamic cellular interactions, niche-specific signaling and transcriptional programs guiding cardiomyocyte maturation. To functionally test prioritized regulators in vivo and at scale, we developed PIP-seq (probe-based indel-detectable Perturb-seq), a high-throughput platform that detects single guide RNA identity, infers gene editing and profiles transcription from fixed nuclei. Applying PIP-seq to the developing postnatal heart, we identified 21 previously uncharacterized regulators of cardiomyocyte maturation, including genes essential for sarcomere assembly, metabolic reprogramming and electrophysiological transitions. Together, our findings define how microenvironmental signals and intrinsic gene programs cooperate to guide heart maturation and establish a broadly applicable framework for functional genomics in complex tissues.

Animals↗

PubMed2026

A Molecularly Anchored Spatial Transcriptomic Framework for Precise CA1-Subiculum Parcellation and Region-Resolved Analysis in Alzheimer's Disease.

BACKGROUND: The precise molecular delineation of the interface between the Subiculum (Sub) and cornu ammonis 1 (CA1) is a challenge in hippocampal research, as conventional cytoarchitectural boundaries are often ambiguous and limit reproducible regional annotation. Here, we developed a molecularly anchored spatial transcriptomic framework to define CA1-Sub regional identities using high-definition spatial transcriptomics (Stereo-seq) and single-nucleus RNA sequencing (snRNA-seq) references. FINDINGS: Using a human hippocampal Stereo-seq dataset from 12 donors, we established a data-driven parcellation framework that defines reproducible molecular features distinguishing CA1 and Sub while capturing the transition between these regions. FN1 was identified as a Sub-enriched marker in a subset of EX_Sub and, together with ETV1 and additional regional markers, enabled molecular assignment of CA1 and Sub identities across datasets. The Sub association of FN1 and ETV1 was further supported by human 10X Genomics spatial transcriptomics, mouse in situ hybridization data, and a mouse spatial transcriptomic dataset. Applying this framework to Alzheimer's disease (AD) tissues revealed region-specific transcriptional alterations across CA1 and Sub, including enrichment of mitochondrial energy metabolism-related transcripts in the Sub, suggesting exploratory transcriptional associations of altered metabolic function. CONCLUSIONS: This study provides a molecularly anchored framework for human CA1-Sub parcellation that complements conventional annotation. By defining regional molecular states while preserving the biological continuum across CA1-Sub interface, this approach enables more consistent regional analysis of human hippocampus tissue across donors, datasets, and disease conditions.

Journal Article↗

PubMed2026

Single-nucleus profiling reveals a core disease signature and cell type-specific vulnerabilities in early Rett syndrome.

Rett syndrome (RTT) is an X-linked neurological disorder caused by MECP2 mutations, creating distinct cellular environments in females (mosaic) versus males (nonmosaic). Despite female patients representing most cases, how mosaicism contributes molecularly to RTT pathogenesis, particularly in presymptomatic stages, remains poorly understood. To address this question, we profiled hippocampal transcriptomes of young female and male RTT mice using bulk and single-nucleus RNA sequencing. We identified a core disease signature of consistently dysregulated genes only in MeCP2- cells across RTT models. Moreover, we uncovered non-cell autonomous effects exclusively in female MeCP2+ excitatory neurons, suggesting that these circuits are more vulnerable early in the mosaic RTT environment. The single-nuclei data also revealed an underappreciated MeCP2- interneuron subtype that had the most transcriptional dysregulation in both male and female RTT hippocampi. Together, these data highlight the different effects of MeCP2 loss on excitatory and inhibitory circuits between the mosaic and nonmosaic environments in early RTT pathogenesis.

Rett Syndrome↗

PubMed2026

Spatiotemporal mapping of tertiary lymphoid structure heterogeneity shapes immune niches and clinical outcomes in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy with limited therapeutic options. The spatial architecture and functional diversity of tertiary lymphoid structures (TLSs) in iCCA remain unclear. Here, we present a multimodal spatial atlas of TLSs and identified intratumoral TLSs (iTLSs) as independent prognostic markers. Bulk proteomic profiling of 214 discovery and 155 validation cases identified a four-tier TLS-based tumor microenvironment classification system and supported development of a TLS-predictive random forest classifier. Imaging mass cytometry revealed that iTLS+ tumors harbor structured immune architectures, where M1-like tissue-resident macrophages (RTMs), dendritic cells, and CXCL13+ CD4+ T cells colocalize to form antigen-presenting neighborhoods (apc-CNs) spatially coupled to TLS core regions (TLScore-CNs). Single-cell spatial transcriptomics further resolved 61 TLSs into 14 spatial niches and defined a pseudotemporal maturation continuum: aggregated, activated, and postactivated. Intraniche communication, primarily mediated by ifnCAFs, iCAFs, and CXCL12+ macrophages, evolved dynamically with maturation. Single-nucleus RNA sequencing combined with Tangram-based spatial mapping revealed CXCL12+ macrophages and iCAFs forming a peripheral band in aggregated TLSs, whereas ifnCAFs infiltrated TLS interiors during activation. These findings define TLS heterogeneity and provide insights for stroma-directed immunotherapy.

Cholangiocarcinoma↗

PubMed2026

Monocarboxylate Transporter 2 (MCT2) Reduction Is Associated with Increased Lung Tumor Growth and Alterations in the Immune Microenvironment in a Subcutaneous Tumor Model.

Monocarboxylate transporter 2 (MCT2; SLC16A7) is a high-affinity pyruvate transporter implicated in cancer metabolism. However, its role in lung cancer progression and the tumor microenvironment remains unclear. This study examined the effects of MCT2 reduction on tumor growth and cell-type-specific transcriptional changes within the tumor microenvironment. MCT2 loxP/loxP mice were crossed with mCre-Tg mice, and MCT2 deletion was induced by tamoxifen. Control (CO) mice received vehicle treatment. TC1 cells (100,000 cells/mouse) were injected subcutaneously, and tumors were harvested after 24 days. Single-nucleus RNA sequencing (snRNA-seq) was performed on isolated tumor nuclei (4000 nuclei/sample; n = 3 per group) using the 10x Genomics Chromium platform. Data were processed with Cell Ranger v3.0.2 and Seurat v5.2.1, followed by differential expression and pathway enrichment analyses integrated with macrophage bulk RNA-seq data. Tumors in mice with systemic MCT2 reduction grew significantly faster than those in control mice, demonstrating an association between host MCT2 reduction and increased tumor growth. Transcriptomic analysis generated high-quality profiles from 6864 CO and 10,055 KO nuclei. Clustering identified 12 cellular populations and cell types. MCT2 reduction altered pathways involved in glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, and fatty acid metabolism across multiple populations. Macrophages showed prominent transcriptional changes, including enrichment of MAPK, PI3K-Akt, IgSF-CAM, ECM, and cytokine-cytokine signaling pathways. These findings were supported by macrophage bulk RNA-seq data. Systemic MCT2 reduction was associated with increased tumor growth and broad transcriptional alterations within the tumor micro-environment. Differences in metabolic and immune-related transcriptional programs, particularly in macrophages, identify potential mechanisms associated with tumor progression that warrant further functional investigation.

Animals↗

PubMed2026

Decoding the landscape of cell-type-specific co-expressed transcription factors in soybean.

Soybean (Glycine max) is an essential source of protein and oil with high nutritional value for human and animal consumption. To enhance our understanding of soybean biology, it is essential to have accurate information regarding the expression of each of its protein-coding genes. Here, we present Tabula Glycine max, a soybean single-cell resolution transcriptome atlas. This atlas comprises single-nucleus RNA-sequencing data from ten different G. max organs and morphological structures constituting the entire soybean plant. These nuclei are grouped into 156 different clusters based on their transcriptomic profiles. The breadth of various organs, tissues and cell types represented in Tabula Glycine max reveals that the pattern of co-expressed transcription factor genes is sufficient to define most cell types based on their function and organ of origin. Defining cell-type-specific co-expressed transcription factor genes offers a new perspective to engineer cell-type-specific programmes and enhance the biology of unique soybean cell types. This cellular resolution and breadth make the Tabula Glycine max an exceptional resource for the plant and soybean communities.

Journal Article↗

PubMed2026

Genetics-Informed Mapping Identifies a CRIM1-Associated Endocardial Inflammatory Remodeling State in Acute Myocardial Infarction.

BACKGROUND Acute myocardial infarction (AMI) reflects inherited susceptibility and inflammatory remodeling, but the cellular contexts linking genetic risk to disease remain unclear. MATERIAL AND METHODS We integrated a meta-transcriptome-wide association study (TWAS) with a human cardiac single-nucleus RNA-sequencing atlas contained 11 individuals (5 AMI and 6 donor) to identify genetics-informed cellular programs. Composite program states were defined by global score quartiles. A fixed 5-gene panel was evaluated for nucleus-level endocardial low-transcriptional-state (Endo_LTS) vs endocardial high-transcriptional-state (Endo_HTS) discrimination within the AMI endocardium using 5-fold leave-1-patient-out cross-validation. Functional follow-up used CRIM1 silencing in hypoxia-treated human induced pluripotent stem cell (hiPSC)-derived endocardial endothelial-like cells and complementary peripheral blood analyses. RESULTS The endocardium exhibited the most prominent infarction-associated increase in TWAS-anchored program activity, with expansion of program-high states and higher CytoTRACE scores. A consensus 5-gene panel (RPS8, PLEC, CFDP1, CRIM1, TNS2) was identified. Among 2163 AMI endocardial nuclei from 5 patients, the state classifier included 364 Endo_LTS and 751 Endo_HTS nuclei; 1048 Endo_MTS nuclei were excluded. Pooled out-of-fold ROC-AUCs ranged from 0.665 to 0.831. The panel also showed discriminatory value in an independent peripheral-blood AMI-vs-control cohort. CRIM1 was prioritized as a candidate linked to the remodeling program. CRIM1 silencing attenuated ACTA2/alpha-SMA, vimentin, LDHA, CCL2, and VEGFA and partially restored CD31, whereas TGF-ß remained elevated. CONCLUSIONS These findings identify a genetics-informed endocardial inflammatory remodeling state in AMI and define a 5-gene surrogate of its activated state. CRIM1 is prioritized as a candidate linked to selected inflammatory, metabolic, and structural outputs. Persistent TGF-b elevation after CRIM1 silencing argues against a simple linear regulatory model and indicates that further mechanistic validation is required.

Humans↗

PubMed2026

A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma.

Pediatric high-grade glioma (pHGG) is an incurable central nervous system malignancy that is a leading cause of pediatric cancer death. While pHGG shares many similarities with adult glioma, it comprises distinct disease entities. In this study, we longitudinally profile a molecularly diverse cohort of 16 pHGG patients through single-nucleus RNA and ATAC sequencing, whole-genome sequencing, and CODEX spatial proteomics to capture the evolution of neoplastic and microenvironmental features during disease progression and treatment. We define a set of core pHGG neoplastic cell states and observe differential tumor-myeloid interactions between malignant cell phenotypes. We find that essential neuromodulators and the interferon response are upregulated post-therapy, implicating them as malignant cell-intrinsic targets. We observe an increase in oligodendrocytes upon progression and that they coordinate spatial motifs with proneural tumor cells. This multiomic atlas of longitudinal pHGG captures features of therapy response and provides a scalable reference for the study of pediatric brain tumors.

Humans↗

PubMed2026

Flexible use of conserved motifs constrains genome access in cell type evolution.

Cell types can be organized into related families, but the regulatory mechanisms that define and maintain these families across deep evolutionary time remain unknown. Here, combining single-nucleus multi-omic sequencing with deep learning to analyse the accessible genomes of two groups of vastly divergent animals including flatworms and vertebrates, we find that hundreds of accessibility-dictating sequence motifs partition into distinct yet conserved sets, or 'vocabularies', each associated with a specific cell type family. However, combinatorial relationships among these motifs preferred by individual cell types are largely species specific. Deep-learning models trained on one species accurately predict family-level chromatin accessibility in distantly related species, albeit frequently rely on different motifs from shared vocabularies to reach convergent predictions. By contrast, models trained on individual cell types within a family lose cross-species predictive power, indicating that the regulatory syntax governing cell type-level identity evolves rapidly. We propose a 'collective maintenance' model in which motif vocabularies defining cell type families are evolutionarily stable, while recombination of these motifs generates cell type-specific regulatory programmes. This suggests that family identity is maintained collectively by large, conserved pools of regulatory factors, analogous to the logic of developmental homology, where character identity persists through network-level conservation despite extensive rewiring.

Journal Article↗

PubMed2026

Precision-Based Filtering Facilitates Cross-Referencing of Conventional and Single-Nucleus Transcriptomes to Identify Time- and Temperature-Sensitive Cell Populations.

Transcriptome analysis via RNA sequencing (RNAseq) has become a ubiquitous method of molecular characterization from whole organisms, dissected tissues, and single cells. These experiments continue to provide an extraordinary volume of data describing molecular states and responses to many conditions. However, standard approaches to RNAseq analysis commonly use expression level filters that eliminate potentially useful data in the service of decreasing noise. Here we describe the implementation of a coefficient of variation-based filter for RNAseq gene expression data. This filter prioritizes consistent data across replicates, allowing lowly-expressed genes with low-variation measurements to be retained for downstream analysis. We show, using two independent Arabidopsis RNAseq datasets, that this filter allows for the inclusion of many more transcription factors than even a low-stringency expression level filter. This effect is independent of sequencing depth. We find that these lowly-expressed genes mark specific cell clusters in our single-nucleus (sn)RNAseq dataset and may facilitate future characterization of currently unknown cell types or states. We further characterize communities of co-expressed genes, sampled across the day at two growth temperatures, in relation to snRNAseq cell clusters, finding evidence for a highly photosynthetic cell population, and a cell state marked by high cell division and translation. These methods can be expanded to RNAseq analysis in many systems, facilitating the construction of more detailed models of tissue-specific gene regulatory networks.

Transcriptome analysis↗

PubMed2026

Single-nucleus profiling of postmortem diffuse midline gliomas identifies mitochondrial biogenesis as a resistance mechanism to imipridone therapy.

BACKGROUND: Imipridone ONC201 is the first FDA-approved therapy for H3K27-altered diffuse midline glioma; however, clinical responses remain limited. Defining tumor-intrinsic determinants and microenvironmental, extrinsic factors that shape sensitivity or resistance to imipridones will identify actionable therapeutic opportunities and inform improved clinical strategies. METHODS: To identify mechanisms of imipridone resistance, we obtained postmortem brain tissue from DMG patients who had received imipridones and/or standard care. Single-nucleus RNA and open-chromatin sequencing were performed on N = 22 cases. Immunofluorescence-based myeloid phenotyping was performed on N = 46 cases. Mitochondrial copy-number analysis was performed on N = 19 cases. Validation of imipridone sensitivity, its effect on mitochondrial density, and its synergy with inhibition of mitochondrial biogenesis were assessed in DMG primary cells. RESULTS: We established a single-cell RNA/open-chromatin atlas from postmortem DMG cases and found imipridone treatment resulting in regressed mesenchymal transition, reduced myeloid-derived suppressive cells, and reversed aberrant H3K27-altered enhancer activity. Resistant tumors showed increased mitochondrial density, turnover, and membrane potential. Mitochondrial biogenesis and PPARGC1A emerged as resistance biomarkers and actionable targets. CONCLUSIONS: These studies implicate mitochondrial biogenesis as a biomarker of imipridone resistance and a focus for the development of combinatorial strategies to provide effective therapeutic options for a challenging pediatric brain tumor.

Humans↗

PubMed2026

Alignment-free integration of single-nucleus ATAC-seq across species with sPYce.

Changes in gene regulation largely contribute to differences in cellular identities and phenotypes between species. Single-nucleus assays for transposase-accessible chromatin with sequencing (snATAC-seq) are an efficient strategy to identify putative gene regulatory elements and provide new insight into evolutionary divergence of regulatory programmes. However, no dedicated framework exists to integrate and compare snATAC-seq data across species, while methods designed for single-cell gene expression data have serious limitations. Here we present sPYce, a cross-species snATAC-seq integration method that relies on sequence composition similarities through k-mer histograms of regulatory regions, removing the need for genome alignments to anchor data from different species. sPYce can embed datasets from multiple species into the same mathematical space and permits further downstream analysis steps. We benchmarked sPYce against existing approaches on two publicly available datasets spanning more than 160 myr of evolution, showing that it successfully uncovers conserved cellular programmes while preserving biologically relevant species-specific differences. By comparing cerebellar development in mice and opossums, sPYce identifies regulatory divergence in granule cell differentiation programmes, particularly driven by nuclear factor 1. As an easy-to-use, alignment-free cross-species snATAC-seq integration approach, sPYce opens new perspectives to compare gene regulatory evolution across species.

Animals↗

PubMed2026

Multiomic single-nucleus profiling reveals cell-type-specific epigenetic and transcriptional dysregulation in major depressive disorder brain.

OBJECTIVE: Major depressive disorder (MDD) is a leading global cause of disability, marked by persistent mood disturbances, cognitive deficits, and changes in prefrontal cortex neural circuitry. In this study, we aimed to define cell-type-specific molecular and regulatory mechanisms underlying MDD by mapping gene-expression and chromatin-accessibility changes in the dorsolateral prefrontal cortex (PFC) (dlPFC). METHODS: Postmortem dlPFC (BA9) tissue from 7 MDD and 8 well-matched controls was analyzed using 10× Genomics snRNA-seq and paired ATAC+RNA multiome sequencing. Sequencing data were processed with Cell Ranger pipelines, nuclei were filtered for quality and doublets/debris, and datasets were integrated and clustered using Seurat/Signac packages. Differential gene expression, chromatin accessibility, and transcription factor motif activity were tested between MDD and controls within each cell type, followed by peak-to-gene linkage and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and PsyGeNET enrichment to interpret dysregulated regulatory mechanisms. RESULTS: A total of 20 distinct clusters encompassing major neuronal and non-neuronal populations were identified. Differential analyses uncovered extensive cell type-specific changes in chromatin accessibility and gene expression, particularly within excitatory layer 5/6 and inhibitory Pvalb neurons, as well as glial and vascular populations. Functional enrichment indicated dysregulation of synaptic organization, neurotransmission, myelination, stress-response, and immune-regulatory pathways across neuronal and non-neuronal cells. Notably, glucocorticoid-responsive transcription factors NR3C1/NR3C2 exhibited conserved regulatory networks implicating stress signaling in MDD pathophysiology. CONCLUSIONS: Together, these findings provide a comprehensive single-nucleus atlas of gene regulation in the MDD PFC, highlighting coordinated dysfunction across neurons, glia, and vascular cells.

Major Depressive Disorder↗

PubMed2026

De Novo TRIO Missense Variants Disrupt Ras-GEF Domains and Cause Congenital Ventriculomegaly and Hydrocephalus.

Congenital hydrocephalus (CH), characterized by congenital ventriculomegaly (CV), affects approximately 0.5-1 per 1000 live births and is a common cause of pediatric neurosurgical intervention, yet its genetic architecture remains incompletely defined. We report a child with syndromic CH requiring cerebrospinal fluid diversion who harbored a pathogenic de novo missense variant in TRIO (c.3232C > T; p.(Arg1078Trp)), a gene previously associated with autosomal dominant neurodevelopmental disorders featuring variable head circumference. This case prompted systematic evaluation of TRIO variation in our CV/CH cohort (2,697 patient-parent trios) using exome sequencing. We identified five additional unrelated probands with de novo TRIO variants, including two novel substitutions affecting the same residue within the Ras-GEF1 domain (p.(Glu1299Lys) and p.(Glu1299Gly)), yielding significant gene-level enrichment for protein-damaging de novo variants (adjusted p = 6.12 × 10-5). All affected individuals exhibited CV, frequently accompanied by developmental delay and additional structural brain abnormalities. In silico structural modeling predicted that associated variants destabilize critical TRIO Ras-GEF domains required for Rho GTPase activation. Analysis of single-nucleus transcriptomic data from the developing human neocortex revealed enrichment of TRIO expression in multipotent progenitor populations. A systematic literature review identified six additional individuals with TRIO de novo variants and reported CV or CH, including an unrelated patient with the same p.(Arg1078Trp) substitution. Together, these findings expand the phenotypic spectrum associated with pathogenic TRIO variation to include CV/CH and support TRIO as a clinically relevant gene in the genetic evaluation of syndromic CV/CH patients.

Humans↗

PubMed2026

Positional grammar of transcription factor binding partitions developmental and stress-response regulation in plants.

Understanding how transcription factor binding site (TFBS) position influences gene regulation remains a fundamental challenge in plants. Here, we integrate conserved multiDAP TFBS maps for 244 transcription factors (TFs) with single-nucleus chromatin accessibility, cell type-resolved gene expression, and hormone-response datasets across Brassicaceae species to determine how TFBS position relates to regulatory function. Although conserved TFBSs are enriched near transcription start sites (TSSs), TSS-proximal accessibility poorly predicts cell type-specific expression. Instead, cell type-specific expression correlates best with conserved TFBSs embedded in cell type-restricted chromatin, with TF family-specific distributions across distal promoters and introns. In contrast, TSS-proximal TFBSs in broadly accessible chromatin are associated with rapid transcriptional responses to abiotic and biotic stress hormones. Coding sequence TFBSs mark a distinct regulatory context in which the same DNA sequence encodes both amino acid sequence and TF motifs, including evidence that CDS-localized ABR1 binding may contribute to repression during hormone response. Finally, distal upstream regions contain conserved multi-family TF clusters with enhancer-like features overlapping rare cell type-specific accessible chromatin and enriched near genes controlling embryonic, meristematic, and hormone-dependent developmental patterning. Together, these results support a positional grammar in which TFBS position and chromatin context jointly partition developmental, stress-responsive, and repressive regulatory output in plants.

Transcription Factors↗

PubMed2025

Combined somatic mutation and transcriptome analysis reveals region-specific differences in clonal architecture in human cortex.

The human cerebral cortex is specialized into regions, but little is known about how human cellular lineages shape cortical regional variation and neuronal cell-type distribution during development. Here, we map single-cell lineages of human cortical regions and neuronal subtypes using >1,000 somatic single-nucleotide variants (sSNVs) identified from deep bulk whole-genome sequencing and analyzed over 25 regions and >72,000 single cells. In the fronto-parietal cortex, sSNVs are rarely restricted, marking neuron-generating clones that disperse into neighboring regions. In contrast, the primary visual cortex harbors 30%-70% more sSNVs than the neighboring secondary visual cortex. Clones at this border exhibit more restricted dispersion, suggesting late developmental lineage segregation. Single-nucleus sSNV and whole-transcriptome analysis reveal glutamatergic neuron clones with modest regional restrictions that share low-mosaic sSNVs with some GABAergic neurons, suggesting a recent dorsal cortical progenitor. Our analysis reveals human-specific cortical lineage patterns, regional differences in clonal patterns, and late divergence of some glutamatergic/GABAergic lineages.

Humans↗

PubMed2025

Decoding ALS from the tail end of RNA.

In this issue of Cell Genomics, McKeever et al.1 generate a single-nucleus transcriptomic atlas of ALS/FTLD brain and reveal widespread alternative polyadenylation changes. Their findings highlight 3' end RNA processing as a central integrator of stress responses, cell-type specificity, and disease susceptibility, offering new mechanistic insight and potential therapeutic directions.

Cell Nucleus↗