bioRxiv : the preprint server for biology最新文献

{"title":"Cellular characterization of the mouse collecting lymphatic vessels reveals that lymphatic muscle cells are the innate pacemaker cells.","authors":"S D Zawieja, G A Pea, S E Broyhill, A Patro, K H Bromert, C E Norton, H J Kim, S K Sivasankaran, M Li, J A Castorena-Gonzalez, B T Drumm, M J Davis","doi":"10.1101/2023.08.24.554619","DOIUrl":"10.1101/2023.08.24.554619","url":null,"abstract":"<p><p>Collecting lymphatic vessels (cLVs) exhibit spontaneous contractions with a pressure-dependent frequency, but the identity of the lymphatic pacemaker cell is still debated. Here we combined immunofluorescence and scRNAseq analyses with electrophysiological methods to examine the cellular constituents of the mouse cLV wall and assess whether any cell type exhibited morphological and functional processes characteristic of pacemaker cells. We employed inducible Cre (iCre) mouse models to target specific cell populations including c-kitCreER ^<i>T2</i> to target interstitial cells of Cajal like cells; <i>PdgfrβCreER</i> ^<i>T2</i> to target pericyte-like cells; <i>PdgfrαCreER</i> ^<i>TM</i> to target CD34⁺ adventitial cells; and <i>Myh11CreER</i> ^<i>T2</i> to target lymphatic muscle cells (LMCs) directly. These inducible Cre lines were crossed to the fluorescent reporter ROSA26mT/mG, the genetically encoded Ca²⁺ sensor GCaMP6f, and the light-activated cation channel rhodopsin2 (ChR2). Only LMCs consistently, but heterogeneously, displayed spontaneous Ca²⁺ events during the diastolic period of the contraction cycle, and whose frequency was modulated in a pressure-dependent manner. Further, optogenetic depolarization with ChR2 only induced propagated contractions in LMCs. Membrane potential recordings in LMCs demonstrated that the rate of diastolic depolarization significantly correlated with contraction frequency. These findings support the conclusion that LMCs, or a subset of LMCs, are responsible for mouse cLV pacemaking.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10473772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10178777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatially defined multicellular functional units in colorectal cancer revealed from single cell and spatial transcriptomics.","authors":"Inbal Avraham-Davidi, Simon Mages, Johanna Klughammer, Noa Moriel, Shinya Imada, Matan Hofree, Evan Murray, Jonathan Chen, Karin Pelka, Arnav Mehta, Genevieve M Boland, Toni Delorey, Leah Caplan, Danielle Dionne, Robert Strasser, Jana Lalakova, Anezka Niesnerova, Hao Xu, Morgane Rouault, Itay Tirosh, Nir Hacohen, Fei Chen, Omer Yilmaz, Jatin Roper, Orit Rozenblatt-Rosen, Mor Nitzan, Aviv Regev","doi":"10.1101/2022.10.02.508492","DOIUrl":"10.1101/2022.10.02.508492","url":null,"abstract":"<p><p>While advances in single cell genomics have helped to chart the cellular components of tumor ecosystems, it has been more challenging to characterize their specific spatial organization and functional interactions. Here, we combine single cell RNA-seq, spatial transcriptomics by Slide-seq, and <i>in situ</i> multiplex RNA analysis, to create a detailed spatial map of healthy and dysplastic colon cellular ecosystems and their association with disease progression. We profiled inducible genetic CRC mouse models that recapitulate key features of human CRC, assigned cell types and epithelial expression programs to spatial tissue locations in tumors, and computationally used them to identify the regional features spanning different cells in the same spatial niche. We find that tumors were organized in cellular neighborhoods, each with a distinct composition of cell subtypes, expression programs, and local cellular interactions. Comparing to scRNA-seq and Slide-seq data from human CRC, we find that both cell composition and layout features were conserved between the species, with mouse neighborhoods correlating with malignancy and clinical outcome in human patient tumors, highlighting the relevance of our findings to human disease. Our work offers a comprehensive framework that is applicable across various tissues, tumors, and disease conditions, with tools for the extrapolation of findings from experimental mouse models to human diseases.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12262820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91351332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronological lifespan extension and nucleotide salvage inhibition in yeast by isonicotinamide supplementation.","authors":"Agata I Kalita, Christopher T Letai, Elisa Enriquez-Hesles, Lindsey N Power, Swarup Mishra, Shekhar Saha, Manikarna Dinda, Dezhen Wang, Pankaj K Singh, Jeffrey S Smith","doi":"10.1101/2021.07.11.451986","DOIUrl":"10.1101/2021.07.11.451986","url":null,"abstract":"<p><p>Isonicotinamide (INAM) is an isomer of the NAD⁺ precursor nicotinamide (NAM) that stimulates the enzymatic activity of Sir2, an NAD⁺-dependent histone deacetylase from the budding yeast, <i>Saccharomyces cerevisiae</i>. Supplementing INAM into growth media promotes the replicative lifespan (RLS) of this single cell organism by maintaining intracellular NAD⁺ homeostasis. INAM also extends yeast chronological lifespan (CLS), but the underlying mechanisms remain largely uncharacterized. To identify interacting genes, a chemical genomics screen of the yeast knockout (YKO) collection was performed for mutants sensitized to growth inhibition by INAM. Significant Gene Ontology (GO) terms included transcription elongation factors, metabolic pathways converging on one-carbon metabolism, and de novo purine biosynthesis, collectively suggesting that INAM may perturb nucleotide metabolism. Indeed, INAM caused dose-dependent depletion of intracellular cytidine, uridine and guanosine, ribonucleosides derived from the breakdown of nucleotide monophosphates by a set of nucleotidases (Phm8, Sdt1, Isn1) or the alkaline phosphatase Pho8. Direct inhibition of recombinant Sdt1 and Phm8 nucleotidase activity by INAM was confirmed <i>in vitro</i>, as was inhibition of alkaline phosphatase activity. Each of these enzymes can also convert nicotinamide mononucleotide (NMN) to nicotinamide riboside (NR), consistent with an accumulation of NMN and NAD⁺ upon inhibition by INAM. Taken together, the findings suggest a model whereby partial impairment of nucleotide salvage pathways can trigger a hormetic stress response that supports enhanced quiescence during chronological aging.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12262425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73751705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cohesin forms fountains at active enhancers in <i>C. elegans</i>.","authors":"Bolaji N Lüthi, Jennifer I Semple, Anja Haemmerli, Saurabh Thapliyal, Kalyan Ghadage, Klement Stojanovski, Dario D'Asaro, Moushumi Das, Nick Gilbert, Dominique A Glauser, Benjamin Towbin, Daniel Jost, Peter Meister","doi":"10.1101/2023.07.14.549011","DOIUrl":"10.1101/2023.07.14.549011","url":null,"abstract":"<p><p>Transcriptional enhancers must locate their target genes with both precision and efficiency. In mammals, this specificity is facilitated by topologically associated domains (TADs), which restrict the enhancer search space through three-dimensional genome organization. In contrast, the nematode genome lacks such TAD-based segmentation despite harboring over 30'000 sequences with chromatin signature characteristic of enhancers, thereby raising the question of how enhancer-promoter specificity is achieved. Using high-resolution Hi-C in <i>C. elegans</i> , we identify distinct 3D chromatin structures surrounding active enhancers, which we term fountains. These structures span 38 kb in average, are unique to active enhancers, and are enriched for the major somatic cohesin complex. Fountains collapse upon <i>in vivo</i> cohesin cleavage, indicating their cohesin dependency. Notably, fountains accumulate topological stress, as evidenced by the enrichment of topoisomerases and the psoralen-binding signature of negatively-supercoiled DNA. Functionally, fountain disassembly correlates with transcriptional upregulation of active enhancer-proximal genes, suggesting that fountains act as spatial repressors of enhancer activity. This repression is particularly pronounced for neuronal genes, including the <i>skn-1/Nrf</i> gene, which becomes upregulated, switches isoform and transcription start site upon cohesin loss in a pair of head neurons. Behaviorally, cohesin cleavage alters nematode movement and foraging behavior, linking enhancer-driven transcriptional changes to neural circuit function and organismal phenotypes, reminiscent of pathologies caused by cohesin mutations in humans. Together, our findings uncover fountains as a novel 3D chromatin feature that modulates enhancer activity in a TAD-less genome, establishing a mechanistic link between genome architecture, gene regulation and behavior.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12262224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84899865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bitesize bundles F-actin and influences actin remodeling in syncytial <i>Drosophila</i> embryo development.","authors":"Anna R Yeh, Gregory J Hoeprich, Anthony McDougal, Bruce L Goode, Adam C Martin","doi":"10.1101/2023.04.17.537198","DOIUrl":"10.1101/2023.04.17.537198","url":null,"abstract":"<p><p>Actin networks undergo rearrangements that influence cell and tissue shape. Actin network assembly and organization is regulated in space and time by a host of actin binding proteins. The <i>Drosophila</i> Synaptotagmin-like protein, Bitesize (Btsz), is known to organize actin at epithelial cell apical junctions in a manner that depends on its interaction with the actin-binding protein, Moesin. Using RNAi, we showed that Btsz functions at earlier, syncytial stages of <i>Drosophila</i> embryo development. Btsz is required to stabilize pseudo-cleavage furrows that prevent metaphase spindle collisions and nuclear fallout prior to cellularization. While previous studies have focused on Btsz function through Moesin, we find that phosphorylated Moesin localized to the nuclear envelope and was not enriched at pseudo-cleavage furrows, suggesting a Moesin- independent function for Btsz in syncytial embryos. Consistent with this, mutants that affected all Moesin binding domain isoforms did not recapitulate pan-isoform Btsz depletion and we find that the C-terminal half of Btsz cooperatively binds to and bundles F-actin. We propose that Synaptotagmin-like proteins directly regulate actin organization during syncytial <i>Drosophila</i> development.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10153138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9768991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local Adaptive Mapping of Karyotype Fitness Landscapes.","authors":"Richard J Beck, Noemi Andor","doi":"10.1101/2023.07.14.549079","DOIUrl":"10.1101/2023.07.14.549079","url":null,"abstract":"<p><p>Despite its critical role in tumor evolution, a detailed quantitative understanding of the evolutionary dynamics of aneuploidy remains elusive. Here we introduce ALFA-K (Adaptive Local Fitness landscapes for Aneuploid Karyotypes), a novel method that infers chromosome-level karyotype fitness landscapes from longitudinal single-cell data. ALFA-K estimates fitness of thousands of karyotypes closely related to observed populations, enabling robust prediction of emergent karyotypes not yet experimentally detected. We validated ALFA-K's performance using synthetic data from an agent-based model and empirical data from in vitro and in vivo passaged cell lines. Analysis of fitted landscapes suggests several key insights: (1) Whole genome doubling facilitates aneuploidy evolution by narrowing the spectrum of deleterious copy number alterations (CNAs); (2) Environmental context and cisplatin treatment significantly modulate the fitness impact of these alterations; (3) Fitness consequences of CNAs are contingent upon parental karyotype; and (4) Chromosome mis-segregation rates strongly influence the predominant karyotypes in evolving populations.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12262491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86808726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probing inter-areal computations with a cellular resolution two-photon holographic mesoscope.","authors":"Lamiae Abdeladim, Uday K Jagadisan, Hyeyoung Shin, Mora B Ogando, Hillel Adesnik","doi":"10.1101/2023.03.02.530875","DOIUrl":"10.1101/2023.03.02.530875","url":null,"abstract":"<p><p>Brain computation depends on intricately connected yet highly distributed neural networks. Due to the absence of the requisite technologies, causally testing fundamental hypotheses on inter-areal processing has remained largely out-of-each. Here we developed the first two photon holographic mesoscope, a system capable of simultaneously reading and writing neural activity patterns with near single cell resolution across large regions of the brain. We demonstrate the precise photo-activation of spatial and temporal sequences of neurons in one or multiple brain areas while reading out the downstream effect in several other regions. We thus establish mesoscale two photon holographic optogenetics as a new platform for mapping functional connectivity and causal interactions across distributed cortical areas with high resolution.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9387607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Awake Imaging of Mouse Deep Brain Microvasculature with Super-resolution Ultrasound Localization Microscopy.","authors":"Yike Wang, Matthew R Lowerison, Zhe Huang, Qi You, Bing-Ze Lin, Daniel A Llano, Pengfei Song","doi":"10.1101/2023.09.01.555789","DOIUrl":"10.1101/2023.09.01.555789","url":null,"abstract":"<p><p>Ultrasound localization microscopy (ULM) is an emerging imaging modality that resolves microvasculature in deep tissues with high spatial resolution. However, existing preclinical ULM applications are largely constrained to anesthetized animals, introducing confounding vascular effects such as vasodilation and altered hemodynamics. As such, ULM quantifications (e.g., vessel diameter, density, and flow velocity) may be confounded by the use of anesthesia, undermining the usefulness of ULM in practice. Here we introduce a method to address this limitation and achieve ULM imaging in awake mouse brain. Pupillary monitoring was used to support the presence of the awake state during ULM imaging. Vasodilation induced by isoflurane was observed by ULM. Upon recovery to the awake state, reductions in vessel density and flow velocity were observed across different brain regions. In the cortex, the effects induced by isoflurane are more pronounced on venous flow than on arterial flow. In addition, serial <i>in vivo</i> imaging of the same animal brain at weekly intervals demonstrated the highly robust longitudinal imaging capability of the proposed technique. The consistency was further verified through quantitative analysis on individual vessels, cortical regions of arteries and veins, and subcortical regions. This study demonstrates longitudinal ULM imaging in the awake mouse brain, which is crucial for many ULM brain applications that require awake and behaving animals.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10508721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41164199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Size tuning of neural response variability in laminar circuits of macaque primary visual cortex.","authors":"Lauri Nurminen, Maryam Bijanzadeh, Alessandra Angelucci","doi":"10.1101/2023.01.17.524397","DOIUrl":"10.1101/2023.01.17.524397","url":null,"abstract":"<p><p>Surround suppression and neural response variability are two widespread cortical phenomena thought to facilitate and impede, respectively, information processing and perception. Typically, manipulations that elicit neural response suppression quench variability, an observation that has led some to suggest that these two phenomena may share a common origin. However, few studies have systematically examined the relationship between surround suppression and variability. Surround suppression is mediated by multiple circuits and mechanisms that depend on the size of the sensory stimulus, and cortical layer. Variability is also laminar dependent. To understand how surround suppression and variability may influence laminar processing, here we have used electrophysiological laminar recordings to examine how neural response variability and the shared variability among neurons are modulated by visual stimulus size across the layers of macaque primary visual cortex (V1). We find that surround suppression does not always quench variability. Instead, variability is tuned for stimulus size in a layer-dependent manner. In all layers, stimulation of the receptive field (RF) reduced neural response variability, and the shared variability among neurons, relative to their pre-stimulus values. As the stimulus was enlarged beyond the RF, to involve the near RF-surround, both neural response variability and shared variability further decreased in infragranular layers, but did not change in granular and supragranular layers. In contrast, larger stimuli involving the far RF-surround increased both neural response variability and shared variability, relative to their value for a stimulus matched to the RF size, in supragranular layers, but decreased them or did not change them in granular and infragranular layers. Surprisingly, we also found that visual stimuli smaller than the RF could increase variability relative to baseline values, particularly in granular and infragranular layers. Our results point to multiple laminar-specific circuits and mechanisms as the source of variability, and call for new models of neural response variability.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ca/32/nihpp-2023.01.17.524397v1.PMC9882156.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9352044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inference of single cell profiles from histology stains with the Single Cell omics from Histology Analysis Framework (SCHAF).","authors":"Charles Comiter, Xingjian Chen, Eeshit Dhaval Vaishnav, Koseki J Kobayashi-Kirschvink, Metamia Ciampricotti, Ke Zhang, Jason Murray, Francesco Monticolo, Jianhuan Qi, Ryota Tanaka, Sonia E Brodowska, Bo Li, Yiming Yang, Scott J Rodig, Angeliki Karatza, Alvaro Quintanal Villalonga, Madison Turner, Kathleen L Pfaff, Judit Jané-Valbuena, Michal Slyper, Julia Waldman, Sebastian Vigneau, Jingyi Wu, Timothy R Blosser, Åsa Segerstolpe, Daniel L Abravanel, Nikhil Wagle, Shadmehr Demehri, Xiaowei Zhuang, Charles M Rudin, Johanna Klughammer, Orit Rozenblatt-Rosen, Collin M Stultz, Jian Shu, Aviv Regev","doi":"10.1101/2023.03.21.533680","DOIUrl":"10.1101/2023.03.21.533680","url":null,"abstract":"<p><p>Tissue biology involves an intricate balance between cell-intrinsic processes and interactions between cells organized in specific spatial patterns, which can be respectively captured by single cell profiling methods, such as single cell RNA-seq (scRNA-seq) and spatial transcriptomics, and histology imaging data, such as Hematoxylin-and-Eosin (H&E) stains. While single cell profiles provide rich molecular information, they can be challenging to collect routinely in the clinic and either lack spatial resolution or high gene throughput. Conversely, histological H&E assays have been a cornerstone of tissue pathology for decades, but do not directly report on molecular details, although the observed structure they capture arises from molecules and cells. Here, we leverage vision transformers and adversarial deep learning to develop the Single Cell omics from Histology Analysis Framework (SCHAF), which generates a tissue sample's spatially-resolved whole transcriptome single cell omics dataset from its H&E histology image. We demonstrate SCHAF on a variety of tissues- including lung cancer, metastatic breast cancer, placentae, and whole mouse pups-training with matched samples analyzed by sc/snRNA-seq, H&E staining, and, when available, spatial transcriptomics. SCHAF generated appropriate single cell profiles from histology images in test data, related them spatially, and compared well to ground-truth scRNA-Seq, expert pathologist annotations, or direct spatial transcriptomic measurements, with some limitations. SCHAF opens the way to next-generation H&E analyses and an integrated understanding of cell and tissue biology in health and disease.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9465051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}