bioRxiv : the preprint server for biology最新文献

{"title":"Neoplastic immune mimicry is a generalizable phenomenon in breast cancer and epithelial CD69 enables early tumor progression.","authors":"Eric B Berens, Sokchea Khou, Elaine Huang, Amber Hoffman, Briana Johnson, Nell Kirchberger, Shamilene Sivagnanam, Nicholas L Calistri, Daniel Derrick, Tiera A Liby, Ian C McLean, Aryn A Alanizi, Furkan Ozmen, Tugba Y Ozmen, Gordon B Mills, E Shelley Hwang, Pepper J Schedin, Hugo Gonzalez, Zena Werb, Laura M Heiser, Lisa M Coussens","doi":"10.1101/2025.01.17.633673","DOIUrl":"https://doi.org/10.1101/2025.01.17.633673","url":null,"abstract":"<p><p>Dedifferentiation programs are commonly enacted during breast cancer progression to enhance tumor cell fitness. Increased cellular plasticity within the neoplastic compartment of tumors correlates with disease aggressiveness, often culminating in greater resistance to cytotoxic therapies or the augmented ability to metastasize to distant organs. Here we report that subpopulations of dedifferentiated neoplastic breast epithelial cells express canonical leukocyte cell surface receptor proteins and have thus named this cellular program \"immune mimicry.\" We document neoplastic cells engaging in immune mimicry within public human breast tumor single-cell RNA-seq datasets, histopathological breast tumor specimens, breast cancer cell lines, as well as in murine transgenic and cell line-derived mammary cancer models. Immune-mimicked neoplastic cells harbor hallmarks of dedifferentiation and appear enriched in treatment-resistant and high-grade breast tumors. We corroborated these observations in aggressive breast cancer cell lines where growth-arresting cytotoxic chemotherapies drove epithelial cells toward immune mimicry. Moreover, in subsequent proof-of-concept studies, we demonstrate that expression of the CD69 leukocyte activation marker by neoplastic cells confers a proliferative advantage that facilitates early tumor growth. We conclude neoplastic breast epithelial cells that upregulate leukocyte surface receptors potentiate malignancy. Moving forward, neoplastic immune mimicry should be evaluated for prognostic utility in breast cancer to determine its stratification potential for patients with increased risks of tumor recurrence, metastasis, and therapeutic resistance.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082951","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":"Scaling down for efficiency: Medium-sized protein language models perform well at transfer learning on realistic datasets.","authors":"Luiz C Vieira, Morgan L Handojo, Claus O Wilke","doi":"10.1101/2024.11.22.624936","DOIUrl":"10.1101/2024.11.22.624936","url":null,"abstract":"<p><p>Protein language models (pLMs) can offer deep insights into evolutionary and structural properties of proteins. While larger models, such as the 15 billion parameter model ESM-2, promise to capture more complex patterns in sequence space, they also present practical challenges due to their high dimensionality and high computational cost. We systematically evaluated the performance of various pLMs across multiple biological datasets to assess the impact of model size on transfer learning. Surprisingly, we found that larger models not necessarily outperform smaller ones, in particular when data is limited. Medium-sized models, such as ESM-2 650M and ESM C 600M, demonstrated consistently good performance, falling only slightly behind their larger counterparts-ESM-2 15B and ESM C 6B-despite being many times smaller. Additionally, we compared various methods of compressing embeddings prior to transfer learning, and we found that mean embeddings consistently outperformed other compression methods. In summary, ESM C 600M with mean embeddings offers an optimal balance between performance and efficiency, making it a practical and scalable choice for transfer learning in realistic biological applications.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142742166","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":"Comparative analysis of <i>Xenopus</i> mesonephric transcriptomics: Conservation of the developmental lineage of nephron stages.","authors":"Mark E Corkins, Adrian Romero-Mora, MaryAnne A Achieng, Nils O Lindström, Rachel K Miller","doi":"10.1101/2025.01.13.632850","DOIUrl":"10.1101/2025.01.13.632850","url":null,"abstract":"<p><p>The mammalian kidney develops in three sequential stages referred to as the pronephros, mesonephros, and metanephros, each developing from the preceding form. All three phases of kidney development utilize epithelized tubules called nephrons, which function to take in filtrate from the blood or coelom and selectively reabsorb solutes the organism needs, leaving waste products to be excreted as urine. The pronephros are heavily studied in aquatic organisms such as zebrafish and Xenopus, as they develop quickly and are functional. The metanephros is a preferred mammalian kidney model, as it best recapitulates human disease. However, very little is known about the mesonephric stage of kidney development in any organism. The pronephros extend to form the mesonephric duct, which ultimately develops into the Wolffian duct in male amniotes. Meanwhile, in organisms that lay their eggs in aquatic environments, the mesonephric kidney is the final form that is generated. Therefore, further understanding of the development and physiology of these kidneys will provide insight into the urogenital system as well as its evolutionary conservation. To gain a better understanding of its structure and cell types, we analyzed the developing mesonephros by in situ and single-cell mRNA sequencing of cells the that make up the developing mesonephros. By comparing these data to those published for the <i>Xenopus</i> pronephros and mammalian metanephros, we were able to evaluate nephron conservation between the three kidney stages.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049322","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":"Caveolin-1 regulates context-dependent signaling and survival in Ewing sarcoma.","authors":"Dagan Segal, Xiaoyu Wang, Hanieh Mazloom-Farisbaf, Divya Rajendran, Erin Butler, Bingying Chen, Bo-Jui Chang, Khushi Ahuja, Averi Perny, Kushal Bhatt, Dana Kim Reed, Diego H Castrillon, Jeon Lee, Elise Jeffery, Lei Wang, Khai Nguyen, Noelle S Williams, Stephen X Skapek, Satwik Rajaram, Reto Fiolka, Khuloud Jaqaman, Gary Hon, James F Amatruda, Gaudenz Danuser","doi":"10.1101/2024.09.23.614468","DOIUrl":"10.1101/2024.09.23.614468","url":null,"abstract":"<p><p>Plasticity is a hallmark function of cancer cells, but many of the underlying mechanisms have yet to be discovered. In this study, we identify Caveolin-1, a scaffolding protein that organizes plasma membrane domains, as a context-dependent regulator of survival signaling in Ewing sarcoma (EwS). Single cell analyses reveal a distinct subpopulation of EwS cells, which highly express the surface marker CD99 as well as Caveolin-1. <i>CD99 High</i> cells exhibit distinct morphology, gene expression, and enhanced survival capabilities compared to <i>CD99 Low</i> cells, both under chemotherapeutic challenge and <i>in vivo.</i> Mechanistically, we show that elevated Caveolin-1 expression in <i>CD99 High</i> cells orchestrates PI3K/AKT survival signaling by modulating the spatial organization of PI3K activity at the cell surface. Notably, CD99 itself is not directly involved in this pathway, making it a useful independent marker for identifying these subpopulations. We propose a model where the <i>CD99 High</i> state establishes a Cav-1-driven signaling network to support cell survival that is distinct from the survival mechanisms of <i>CD99 Low</i> cells. This work reveals a dynamic state transition in EwS cells and highlights Caveolin-1 as a key driver of context-specific survival signaling.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879409","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":"Associations between prenatal distress, mitochondrial health, and gestational age: findings from two pregnancy studies in the USA and Turkey.","authors":"Qiuhan Huang, David Shire, Fiona Hollis, Sameera Abuaish, Martin Picard, Catherine Monk, Elif Aysimi Duman, Caroline Trumpff","doi":"10.1101/2024.10.16.618719","DOIUrl":"10.1101/2024.10.16.618719","url":null,"abstract":"<p><p>Objective This study examined associations between mitochondrial markers-circulating cell-free mitochondrial DNA (cf-mtDNA) and Growth Differentiation Factor-15 (GDF15)-with maternal distress and pregnancy outcomes. Method Participants were drawn from two pregnancy studies, EPI (N=187, USA) and BABIP (N=198, Turkey). Plasma cf-mtDNA and GDF15 levels were quantified using qPCR and ELISA assays. Results Plasma cf-mtDNA levels did not significantly vary across pregnancy, while plasma GDF15 levels increased from early to late pregnancy and decreased postpartum. Late 2nd trimester plasma GDF15 was negatively correlated with pre-pregnancy BMI (p=0.035) and gestational age (p=0.0048) at birth. Early 2nd trimester maternal distress was associated with lower cf-mtDNA (p<0.05) and a trend for lower GDF15. Higher pre-pregnancy BMI and late-pregnancy maternal distress were linked to smaller postpartum GDF15 declines in EPI (p<0.05). Conclusion This study reveals distinct plasma cf-mtDNA and GDF15 patterns during the perinatal period, linking mitochondrial markers to maternal distress and pregnancy outcomes.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11507865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515990","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":"High resolution imaging and interpretation of three-dimensional RPE sheet structure.","authors":"Kevin J Donaldson, Micah A Chrenek, Jeffrey H Boatright, John M Nickerson","doi":"10.1101/2024.12.04.626881","DOIUrl":"10.1101/2024.12.04.626881","url":null,"abstract":"<p><p>The retinal pigment epithelium (RPE), a monolayer of pigmented cells, is critical for visual function through its interaction with the neural retina. In healthy eyes, RPE cells exhibit a uniform hexagonal arrangement, but under stress or disease, such as age-related macular degeneration (AMD), dysmorphic traits like cell enlargement and apparent multinucleation emerge. Multinucleation has been hypothesized to result from cellular fusion, a compensatory mechanism to maintain cell to cell contact, barrier function, and conserve resources in unhealthy tissue. However, traditional two-dimensional (2D) imaging using apical border markers alone may misrepresent multinucleation due to the lack of lateral markers. We present high-resolution confocal images enabling three-dimensional (3D) visualization of apical (ZO-1) and lateral (alpha-catenin) markers alongside nuclei. In two RPE damage models, we find that seemingly multinucleated cells are often single cells with displaced neighboring nuclei and lateral membranes. This emphasizes the need for 3D analyses to avoid misinterpreting multinucleation and underlying fusion mechanisms. Lastly, images from the NaIO3 oxidative damage model reveal variability in RPE damage, with elongated, dysmorphic cells showing increased ZsGreen reporter protein expression driven by EMT-linked CAG promoter activity, while more regular RPE cells displayed somewhat reduced green signal more typical of epithelial phenotypes.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11643093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831812","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":"An iPSC model of fragile X syndrome reflects clinical phenotypes and reveals m ⁶ A- mediated epi-transcriptomic dysregulation underlying synaptic dysfunction.","authors":"Lu Lu, Avijite Kumer Sarkar, Lan Dao, Yanchen Liu, Chunlong Ma, Phyo Han Thwin, Xuyao Chang, George Yoshida, Annie Li, Cenjing Wang, Crace Westerkamp, Lauren Schmitt, Maag Chelsey, Monzon Stephanie, Yu Zhao, Yaping Liu, Xiong Wang, Ling-Qiang Zhu, Dan Liu, Jason Tchieu, Makoto Miyakoshi, Haining Zhu, Christina Gross, Ernest Pedapati, Nathan Salomonis, Craig Erickson, Ziyuan Guo","doi":"10.1101/2024.10.14.618205","DOIUrl":"10.1101/2024.10.14.618205","url":null,"abstract":"<p><p>Fragile X syndrome (FXS), the leading genetic cause of intellectual disability, arises from <i>FMR1</i> gene silencing and loss of the FMRP protein. N6-methyladenosine (m ⁶ A) is a prevalent mRNA modification essential for post-transcriptional regulation. FMRP is known to bind to and regulate the stability of m ⁶ A-containing transcripts. However, how loss of FMRP impacts on transcriptome-wide m ⁶ A modifications in FXS patients remains unknown. To answer this question, we generated cortical neurons differentiated from induced pluripotent stem cells (iPSC) derived from healthy subjects and FXS patients. In electrophysiology recordings, we validated that synaptic and neuronal network defects in iPSC-derived FXS neurons corresponded to the clinical EEG data of the patients from which the corresponding iPSC line was derived. In analysis of transcriptome-wide methylation, we show that FMRP deficiency led to increased translation of m ⁶ A writers, resulting in hypermethylation that primarily affecting synapse-associated transcripts and increased mRNA decay. Conversely, in the presence of an m ⁶ A writer inhibitor, synaptic defects in FXS neurons were rescued. Taken together, our findings uncover that an FMRP-dependent epi-transcriptomic mechanism contributes to FXS pathogenesis by disrupting m ⁶ A modifications in FXS, suggesting a promising avenue for m ⁶ A- targeted therapies.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11507714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515983","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":"High-throughput Mucus Microrheology for Phenotyping and Disease Modeling.","authors":"Feng Ling, Ayse Tugce Sahin, Bernardo Miller Naranjo, Stefano Aime, Doris Roth, Niels Tepho, Andrea S Vendrame, Ellen Emken, Marion Kiechle, Yohannes Tesfaigzi, Oliver Lieleg, Janna Nawroth","doi":"10.1101/2025.01.09.632077","DOIUrl":"10.1101/2025.01.09.632077","url":null,"abstract":"<p><p>Mucus plays an integral role for the barrier function of many epithelial tissues. In the human airways, mucus is constantly secreted to capture inhaled microbes and pollutants and cleared away through concerted ciliary motion. Many important respiratory diseases exhibit altered mucus flowability and impaired clearance, contributing to respiratory distress and increased risk of infections. Understanding how mucus rheology changes during disease progression and in response to treatments is thus of great interest for subtyping patients and tailoring treatments, probing disease mechanisms, and tailoring therapies; however, basic research of mucus rheology is greatly hampered by the lack of scalable and user-friendly rheometry assays for the small volumes of mucus typically produced by in vitro respiratory models and in clinical ex vivo settings. To address this challenge, we developed a streamlined, high-throughput protocol leveraging Differential Dynamic Microscopy (DDM) to reliably measure the frequency-dependent microrheology of minuscule (3-10 <i>µ</i> L) mucus samples using standard epifluorescence microscopy. Our method does not require time-consuming user-interventions common in particle tracking routines and measures microrheology at the time scale of mucus relaxation (1-20s), hence greatly reducing assay time. We demonstrate the successful application of our method in mucus samples harvested from state-of-the-art air-liquid-interface (ALI) human respiratory cultures to assess mucus rheology in airway disease models and different culture conditions. To show that our approach equally applies to other types and sources of human mucus, we also validated our method with clinical samples of cervical mucus. We envision that our method can be seamlessly adopted by non-expert users, without the need for specialized equipment or extensive training, to study diseases and their treatments in the respiratory, intestinal, reproductive and other mucosal organ systems. This advancement opens up new avenues for large-scale studies, providing new insights into the role of mucus rheology which was previously limited by data accessibility and resource constraints.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048522","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":"Investigation of All Disease-Relevant Lysine Acetylation Sites in α-Synuclein Enabled by Non-canonical Amino Acid Mutagenesis.","authors":"Marie Shimogawa, Ming-Hao Li, Grace Shin Hye Park, Jennifer Ramirez, Hudson Lee, Paris R Watson, Swati Sharma, Zongtao Lin, Chao Peng, Benjamin A Garcia, David W Christianson, Elizabeth Rhoades, David Eliezer, E James Petersson","doi":"10.1101/2025.01.21.634178","DOIUrl":"https://doi.org/10.1101/2025.01.21.634178","url":null,"abstract":"<p><p>Aggregates of α-synuclein (αS) are hallmarks of synucleinopathies, including Parkinson's Disease (PD) and Multiple System Atrophy (MSA). We have recently shown that αS lysine acetylation in the soluble monomer pool varies between healthy controls, PD, and MSA patients. To study the effects of lysine acetylation at all disease-relevant sites of αS, we first compared production of acetylated αS through either native chemical ligation or non-canonical amino acid (ncAA) mutagenesis. Since yields were comparable, ncAA mutagenesis was deemed superior for scanning many acetylation sites. We expressed and purified 12 disease-relevant variants and studied their binding to membranes as well as their aggregation propensities, and found that acetylation of lysine 12, 43, and 80 had particularly strong effects. To understand the implications for acetylation of monomeric αS found in healthy cells, we performed NMR experiments to study protein conformation and fluorescence correlation spectroscopy experiments to quantify lipid binding. We also investigated the effects of acetylation at lysine 12, 43, and 80 on fibril seeding in neurons. Collectively, our biochemical and cell biological investigations indicated that acetylation of K ₈₀ could inhibit aggregation without conferring negative effects on monomer function in healthy cells. Therefore, we studied the structures of fibrils with K ₈₀ acetylation through cryo-electron microscopy to uncover the structural basis for these effects. Finally, we identified inhibition of HDAC8 as a way of potentially increasing acetylation at K ₈₀ and other inhibitory sites for therapeutic benefit.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083036","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":"Distinct mechanisms for panoramic and landmark-based view integration in human scene-selective cortex.","authors":"Linfeng Tony Han, Russell A Epstein","doi":"10.1101/2025.01.24.634774","DOIUrl":"https://doi.org/10.1101/2025.01.24.634774","url":null,"abstract":"<p><p>To encode a cognitive map of an environment, a navigating agent must be able to integrate across disparate perceptual views corresponding to the same place. There are two ways that this can be done. First, the agent might integrate across the panorama of views obtainable at a single vantage point. Second, they might integrate across views of a distal location containing a landmark that is visible from multiple vantage points. Guided by previous work, we tested the hypothesis that these two viewpoint-integration processes would be mediated by different neuroanatomical substrates. Male and female human participants were familiarized with a route through a virtual city, along which they closely viewed 24 storefronts that were pairwise associated, either by being located on different buildings directly across the street from each other (same-panorama condition) or by being located on different sides of the same building facing different streets (same-landmark condition). They were then scanned with fMRI while viewing the storefronts in isolation and performing a spatial memory task. Multivoxel pattern analysis revealed a functional distinction between two scene-selective regions: the retrosplenial complex (RSC) showed a significant association effect for same-panorama storefronts, whereas the parahippocampal place area (PPA) showed a significant association effect for same-landmark storefronts. Panoramic association effects were also observed in several other dorsal-stream regions within the medial and lateral parietal lobe. These results demonstrate the existence of two neural mechanisms for integrating across views to represent places as either the observer's location (same panorama) or the observed location (same landmark).</p><p><strong>Significance statement: </strong>An important component of spatial navigation is the ability to integrate across disparate views corresponding to the same place. Here we tested the idea that there are two such integration mechanisms in the human brain. Participants were familiarized with a virtual city and then scanned with fMRI while viewing storefronts from that city. Using multivariate pattern analysis, we find that the retrosplenial complex (RSC) and other parietal regions encode panoramas of views observed from specific locations, whereas the parahippocampal place area (PPA) encodes sets of views corresponding to specific landmarks. These results reveal two anatomically separated mechanisms for integrating views into places, thus advancing our understanding of how the brain forms cognitive maps of spatial environments.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082402","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}