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Live-cell imaging and ultrastructure expansion microscopy reveal the dynamic intracellular life cycle of the microsporidian parasite Encephalitozoon intestinalis. 活细胞成像和超微结构扩增显微镜揭示了肠囊虫胞内的动态生命周期。
bioRxiv : the preprint server for biology Pub Date : 2026-10-08 DOI: 10.64898/2026.09.25.754474
Kacie L McCarty, Sabrina Absalon, Gira Bhabha, Damian C Ekiert
{"title":"Live-cell imaging and ultrastructure expansion microscopy reveal the dynamic intracellular life cycle of the microsporidian parasite <i>Encephalitozoon intestinalis</i>.","authors":"Kacie L McCarty, Sabrina Absalon, Gira Bhabha, Damian C Ekiert","doi":"10.64898/2026.09.25.754474","DOIUrl":"10.64898/2026.09.25.754474","url":null,"abstract":"<p><p>Microsporidia are divergent fungal pathogens that infect a wide range of hosts. Microsporidia have evolved highly reduced genomes, resulting in the loss of many metabolic pathways. <i>Encephalitozoon intestinalis</i> is a human-infecting microsporidian species with the smallest known eukaryotic genome (2.3 Mbp). As an obligate intracellular parasite, <i>E. intestinalis</i> is dependent on its host for replication. Our current understanding of <i>E. intestinalis</i> cell biology remains limited. This is largely due to genetic intractability, which has made live-cell imaging challenging, and its small size (~2 μm), which is within the diffraction limit of conventional microscopy. Here we develop a live-cell imaging technique, \"silhouette microscopy\", that does not rely on genetic manipulation of microsporidia, and enables us to study the live cell dynamics of <i>E. intestinalis</i> replication in host cells, from entry to exit. We report the timing of cell division, kinetics of the parasite life cycle, and dynamics of the parasitophorous vacuole within which <i>E. intestinalis</i> resides. The parasitophorous vacuole undergoes frequent fission and fusion, and ultimately ruptures to facilitate parasite release from the host cell. Silhouette microscopy provides an excellent platform to study the life cycle dynamics of other microsporidian species as well as other genetically intractable intracellular pathogens. To gain a higher resolution understanding into the cell biology of <i>E. intestinalis</i> development, we performed ultrastructure expansion microscopy (U-ExM) on infected cells. U-ExM reveals the organization of the <i>E. intestinalis</i> cytoskeleton and development of the specialized invasion organelle, the polar tube. The combination of live-cell imaging and U-ExM provide a platform to study the <i>E. intestinalis</i> life cycle, and sheds light on the dynamics and cell biology of <i>E. intestinalis</i> in host cells.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13622293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122183","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}
引用次数: 0
Shear Strain Stiffening in Cartilage is Governed by a Mechanical Phase Transition. 软骨中的剪切应变硬化是由力学相变控制的。
bioRxiv : the preprint server for biology Pub Date : 2026-10-08 DOI: 10.64898/2026.09.28.751808
Japheth Omonira, Joshua D Clugston, Anna R Barth, Stephen J Thornton, James P Sethna, Moumita Das, Lawrence J Bonassar, Itai Cohen
{"title":"Shear Strain Stiffening in Cartilage is Governed by a Mechanical Phase Transition.","authors":"Japheth Omonira, Joshua D Clugston, Anna R Barth, Stephen J Thornton, James P Sethna, Moumita Das, Lawrence J Bonassar, Itai Cohen","doi":"10.64898/2026.09.28.751808","DOIUrl":"10.64898/2026.09.28.751808","url":null,"abstract":"<p><p>Large shear deformation in cartilage can lead to tissue failure and injury, which are often precursors to diseases such as post-traumatic osteoarthritis. Under shear, cartilage strain-stiffens prior to failure, which makes stiffening an important indicator of changes to the loading of the extracellular matrix that gives rise to this tissue's properties. While a variety of stiffening mechanisms ranging from uncrimping to fiber-alignment have been explored, whether such mechanisms apply to the depth dependent shear strain stiffening in articular cartilage remains poorly understood. Here, we present experiments and theory that support the idea that the strain-stiffening behavior is caused by a mechanical phase transition from a random isotropic network whose mechanics arise primarily from bending-dominated modes to one where the mechanics arise from stretching-dominated modes. Indeed, consistent with network model predictions, we find that stress-strain data for all depths can be collapsed onto a single universal curve that diverges at a depth-dependent critical strain. These results show that increasing the local concentration of collagen, which constitutes the primary load-bearing network in cartilage, decreases the critical strain at which the strain-stiffening transition occurs, while increasing the low-strain elastic modulus. Furthermore, we demonstrate that bulk compression leads to a higher critical strain and decreased low-strain elastic modulus. Network simulations capture this rich behavior, and indicate that under compression the network collapses, which allows for larger strains before the transition from bending-dominated to stretching-dominated mechanics occurs. Collectively, these findings shed light on the roles that tissue composition and axial strain play in the mechanisms that organize how articular cartilage stiffens during the lead-up to injury.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169027","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}
引用次数: 0
Survey of nucleotide-specific Rab GTPase interactions reveals multiple Rab effectors. 对核苷酸特异性Rab GTPase相互作用的调查揭示了多个Rab效应物。
bioRxiv : the preprint server for biology Pub Date : 2026-10-08 DOI: 10.64898/2026.09.15.751902
Tabitha A Peterson, Christopher P Ptak, Mark A Stamnes, Robert C Piper
{"title":"Survey of nucleotide-specific Rab GTPase interactions reveals multiple Rab effectors.","authors":"Tabitha A Peterson, Christopher P Ptak, Mark A Stamnes, Robert C Piper","doi":"10.64898/2026.09.15.751902","DOIUrl":"10.64898/2026.09.15.751902","url":null,"abstract":"<p><p>Rab GTPases control myriad molecular functions by acting as a nucleotide-dependent switch for protein-protein interactions localized in discrete subcellular regions (Zerial and McBride, 2001). Finding additional molecular roles for Rab GTPases depends on expanding the identification of their nucleotide-dependent interactions. Here we compare the interactome of Rab GTPases using a comprehensive large-scale yeast 2-hybrid approach powered by quantitative high-throughput sequencing, which was used to find interactions of the major mammalian Rab isoforms locked in a GDP or GTP conformation. These data revealed an expanded set of interactions specific for GTP-bound Rab proteins, with many known Rab effectors capable of binding a wider repertoire of Rab partners than previously appreciated. We also identified the RGS domain of SNX13 and SNX14 as a new Rab GTPase-binding domain that may bridge these ER-localized proteins with Rab5 and Rab11 endosomal compartments, respectively.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149032771","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}
引用次数: 0
Reversing aging-like 3D genome disorganization in a Drosophila interphase model. 在果蝇间期模型中逆转衰老样三维基因组解体。
bioRxiv : the preprint server for biology Pub Date : 2026-10-07 DOI: 10.64898/2026.07.16.739007
Alexey V Onufriev, Junkai Zhang, Igor V Sharakhov, Igor S Tolokh
{"title":"Reversing aging-like 3D genome disorganization in a <i>Drosophila</i> interphase model.","authors":"Alexey V Onufriev, Junkai Zhang, Igor V Sharakhov, Igor S Tolokh","doi":"10.64898/2026.07.16.739007","DOIUrl":"10.64898/2026.07.16.739007","url":null,"abstract":"<p><p>Recent experimental evidence suggests that aging may arise from the progressive deterioration of the epigenetic landscape, while reversing the trend can result in cell and tissue rejuvenation. A mechanistic understanding of how restoration of a key component of this landscape - the 3D structure of the genome - can be accomplished is lacking. Here we investigate the lamina-dependent disruption and recovery of the 3D architecture of the <i>Drosophila melanogaster</i> genome at topologically associating domains (TADs) resolution (~ 100 kb), using a model of the entire nucleus; weakening of chromatin-lamina interactions mimics a loss of chromatin organization associated with aging. We characterize this loss using the Shannon entropy of the appropriately normalized Hi-C contact and by deterioration of the chromosome territories. Our main finding is that increase in Hi-C map disorder and deterioration of chromosome territories induced by lamina depletion are largely reversible when the wild-type (WT)-like Lamina-associated domain (LAD)-nuclear-envelope interactions are restored; the original and recovered conformational states of chromatin are essentially indistinguishable by the bulk Hi-C contact matrix, and the recovered WT state of chromatin remains stable. The recovery is robust: we find that the WT-like 3D architecture can also be recovered from a more severely perturbed lamina-depleted and compartment-disrupted state, in which all attractive interactions have been switched off. The direct experimentally testable prediction is that the restoration of functional LAD-lamina interactions will promote recovery of the WT-like 3D chromatin architecture after lamina-dependent architectural disruption. We further hypothesize that lamin restoration may increase lifespan of the fruit fly and improve other aging-associated phenotypes through the recovery of young-like LAD-lamina attachments.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13419808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148650352","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}
引用次数: 0
Thermal pre-treatment of algal symbiont species differentially affects coral development. 藻类共生物种的热预处理对珊瑚发育的影响是不同的。
bioRxiv : the preprint server for biology Pub Date : 2026-10-07 DOI: 10.64898/2026.07.24.739192
Maria Ruggeri, Samuel A Bedgood, Jun B Cai, Jennifer Qian, Federica Montesanto, Mark McCauley, Grayce E Dyer, Ayobami Oluokun, Mojibola Fowowe, Odunayo Oluokun, Yehia Mechref, Saki Harii, Sandra Loesgen, Virginia M Weis
{"title":"Thermal pre-treatment of algal symbiont species differentially affects coral development.","authors":"Maria Ruggeri, Samuel A Bedgood, Jun B Cai, Jennifer Qian, Federica Montesanto, Mark McCauley, Grayce E Dyer, Ayobami Oluokun, Mojibola Fowowe, Odunayo Oluokun, Yehia Mechref, Saki Harii, Sandra Loesgen, Virginia M Weis","doi":"10.64898/2026.07.24.739192","DOIUrl":"10.64898/2026.07.24.739192","url":null,"abstract":"<p><p>The foundation of coral reef ecosystems centered around the nutritional relationship between corals and intracellular algal symbionts. Although these symbioses are highly obligate for coral hosts, many partnerships are re-established anew with each coral generation. Furthermore, climate change destabilizes the symbiosis, and the cellular mechanisms underlying successful symbiont colonization of hosts and host development, and how they are affected by thermal stress are poorly understood. Here, we explored the effect of algal species and thermal treatments on symbiont and host cell proliferation by offering Acropora tenuis larvae one of four algal species pre-exposed to elevated or ambient temperature. In addition, we characterized the cell-surface glycome of each species-temperature combination to understand its role in symbiont recognition and proliferation. We found that thermal pre-treatment negatively affected algal photosynthetic efficiency and initial symbiont density in hosts, but did not affect symbiont colonization rate or cell proliferation. In contrast, host cell proliferation was affected in a species-specific manner. Thermal pre-treatment of B. minutum and D. trenchii negatively affected host cell proliferation compared to control symbionts, whereas thermal treatment of S. microadriaticum did not affect developmental outcomes. Further, uptake of thermally pre-treated D. trenchii decreased host cell proliferation below that of larvae not offered any symbionts, indicating that this relationship is costly to host development despite the high thermal tolerance of this species. Algal surface glycan composition varied across species but not by thermal pre-treatment, suggesting reductions in density of thermally pre-treated algae may be due to changes in physiology rather than altered surface chemistry. Further, variation in glycan abundance across species did not track differences in colonization rate or symbiont density, hinting towards a smaller role of glycans in host-symbiont specificity.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148804544","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}
引用次数: 0
Pupil size and pupil change correlate with distinct cortical neurochemical systems across the adult lifespan. 瞳孔大小和瞳孔变化与成人一生中不同的皮层神经化学系统相关。
bioRxiv : the preprint server for biology Pub Date : 2026-10-07 DOI: 10.64898/2026.08.24.746786
Elizabeth Riley, Eve De Rosa, Adam Anderson
{"title":"Pupil size and pupil change correlate with distinct cortical neurochemical systems across the adult lifespan.","authors":"Elizabeth Riley, Eve De Rosa, Adam Anderson","doi":"10.64898/2026.08.24.746786","DOIUrl":"10.64898/2026.08.24.746786","url":null,"abstract":"<p><p>Pupillometry is often used as a proxy for locus coeruleus (LC) activity but whether this relationship changes across the lifespan is unknown. We collected simultaneous pupillometry and multi-echo fMRI in 89 adults aged 19-78 during a visual oddball task. Oddball-evoked pupillary responses were present in all age groups and largest in middle age. Oddball-evoked LC BOLD responses were detected only in younger adults and did not predict individual pupillary responses. Pupil size and its first derivative (pupil change) correlated with whole-brain BOLD on distinct timescales and in distinct spatial patterns. Against 19 PET maps, pupil derivative coupling correlated uniquely with norepinephrine transporter (NET) density, and pupil size-unique coupling with μ-opioid, cannabinoid CB1, and glutamatergic mGluR5 density. Only the pupil derivative-NET relationship weakened with age, though it remained significant in every group. Pupil size and pupil change therefore carry different information, and only pupil change correlates with activity in NET-rich regions across the lifespan.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149032766","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}
引用次数: 0
Reciprocal control of the stomach and intestine by viscerosensory neurons in caudal brainstem. 尾侧脑干脏器感觉神经元对胃和肠的相互控制。
bioRxiv : the preprint server for biology Pub Date : 2026-10-07 DOI: 10.64898/2026.09.21.753299
Naz Dundar, Ilayda Alkislar, Brooke C Jarvie, Ho Namkung, Kathryn Xie, Mahekdeep Kaur, Queenie Li, Anagh S Ravi, Alejandro Lopez, Antionette Spina, Longhui Qui, Truong Ly, Jun Oh, Kevin Yackle, Zachary A Knight
{"title":"Reciprocal control of the stomach and intestine by viscerosensory neurons in caudal brainstem.","authors":"Naz Dundar, Ilayda Alkislar, Brooke C Jarvie, Ho Namkung, Kathryn Xie, Mahekdeep Kaur, Queenie Li, Anagh S Ravi, Alejandro Lopez, Antionette Spina, Longhui Qui, Truong Ly, Jun Oh, Kevin Yackle, Zachary A Knight","doi":"10.64898/2026.09.21.753299","DOIUrl":"10.64898/2026.09.21.753299","url":null,"abstract":"<p><p>Digestion requires precisely timed transit of food through the gastrointestinal tract. Here we show that emptying of food from the stomach occurs in discrete pulses, separated by pauses that allow the proximal duodenum to clear before the next bolus arrives. By combining X-ray fluoroscopy of the gut with calcium imaging of the brainstem, we identify a population of neurons defined by expression of neuropeptide FF (NPFF) that tracks these duodenal dynamics. Stimulation of NPFF neurons induces a coordinated response that inhibits gastric emptying and accelerates intestinal transit, thereby clearing the proximal intestine for the next bolus of food. These neurons also bidirectionally control food intake through cholinergic signaling in the gut. These findings reveal a mechanism by which brainstem transforms the sensory detection of nutrients in the duodenum into the opposing control of the stomach and intestine. They also establish an experimental approach for dissecting gut-brain signaling in behaving animals.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169764","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}
引用次数: 0
Modulation of gp130 Cytokine Receptor Family by Herpes Simplex Virus 1 as a Strategy for Immune Evasion. 单纯疱疹病毒1对gp130细胞因子受体家族的调节作为免疫逃避策略
bioRxiv : the preprint server for biology Pub Date : 2026-10-07 DOI: 10.64898/2026.10.06.757054
Kimberly Foster-Lemieur, Sreenath Muraleedharan Suma, Meenu Ajith, Maria Kalamvoki
{"title":"Modulation of gp130 Cytokine Receptor Family by Herpes Simplex Virus 1 as a Strategy for Immune Evasion.","authors":"Kimberly Foster-Lemieur, Sreenath Muraleedharan Suma, Meenu Ajith, Maria Kalamvoki","doi":"10.64898/2026.10.06.757054","DOIUrl":"10.64898/2026.10.06.757054","url":null,"abstract":"&lt;p&gt;&lt;p&gt;HSV-1 is a neurotropic human pathogen that establishes lifelong latency in sensory neurons. Periodic reactivation causes mucocutaneous lesions and, in some cases, severe corneal and neurological disease. While HSV-1 utilizes numerous viral proteins to extensively reprogram host signaling pathways and evade antiviral responses, how it alters host cytokine receptor networks remains poorly understood. Here, we demonstrate that HSV-1 infection selectively downmodulates multiple members of the gp130 (glycoprotein 130) cytokine receptor family, including gp130, Oncostatin M receptor β (OSMR-β), and leukemia inhibitory factor receptor (LIFR), while sparing IL-6Ra and CNTFRa (Ciliary Neurotrophic Factor Receptor). Because gp130 is the central signaling component of the IL-6 cytokine family and mediates JAK/STAT3 activation, its elimination likely represents a viral strategy to suppress inflammatory and antiviral signaling. Consistent with this, HSV-1 does not induce IL-6 mRNA expression in productively infected cells, suggesting coordinated inhibition of both cytokine production and receptor availability. Mechanistically, we found that the viral RNase VHS is at least partially responsible for gp130 family receptor downmodulation, likely in combination with virus-induced endocytosis/degradation pathways. Functionally, activation of gp130 signaling significantly impairs HSV-1 infection, demonstrating that suppression of antiviral cytokine responses is critical for virus replication. Finally, we determined that CNTF causes reactivation of latent HSV-1 using the LUHMES &lt;i&gt;in vitro&lt;/i&gt; latency model, illustrating CNTFRa signaling contribution to latency and reactivation. A similar effect has been reported for IL-6. Together, these findings reveal a previously unrecognized immune evasion mechanism by which HSV-1 remodels gp130 cytokine signaling to promote infection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Successful infection requires HSV-1 to overcome innate immunity that would otherwise restrict viral replication and spread. However, how the virus alters cytokine receptor signaling at the cell surface remains poorly understood. The gp130 family of cytokine receptors represents an important signaling network that governs immunity. These receptors mediate responses to IL-6 family cytokines and regulate antiviral defense, inflammation, cell survival, and neuronal function. Because individual gp130 family receptors can initiate distinct responses, understanding how HSV-1 alters these receptors is important for defining how the virus reshapes host cytokine networks. Here, we report that HSV-1 downmodulates specific gp130 family members to evade host antiviral and inflammatory signaling. However, CNTFRa, a receptor vital to neuronal function is preserved. Characterizing this distinct layer of HSV-1 immune evasion broadens our understanding of virus-host interactions and highlights novel signaling pathways that can be targeted to maximize host antiviral defenses.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198708","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}
引用次数: 0
Tunable population diversity through a noise-driven differentiation switch. 调节网络模型揭示了神经元-胶质细胞比例控制中信号加性集成的噪声门控拨动开关。
bioRxiv : the preprint server for biology Pub Date : 2026-10-06 DOI: 10.1101/2025.09.20.677552
Jialong Jiang, Sisi Chen, Jong H Park, Tiffany Tsou, Vickie Yang, Paul Rivaud, Matt Thomson
{"title":"Tunable population diversity through a noise-driven differentiation switch.","authors":"Jialong Jiang, Sisi Chen, Jong H Park, Tiffany Tsou, Vickie Yang, Paul Rivaud, Matt Thomson","doi":"10.1101/2025.09.20.677552","DOIUrl":"10.1101/2025.09.20.677552","url":null,"abstract":"<p><p>During development, combinatorial signals modulate progenitor differentiation to build populations of diverse cell types. Classical deterministic fate-control circuits focus on stable commitment but do not explain how a diverse cell population is generated and tuned by signals. Here, using single-cell RNA-seq profiling of neural progenitor cells (NPCs) upon combinatorial signal inputs, we identify a candidate circuit-level mechanism for controlling cell type compositions through an annealed noise-driven switch. With 40 signaling conditions, we show that combinatorial signal inputs modulate the neuronal-glial population proportions following a simple log-linear model. Regulatory network models built by D-SPIN quantitatively capture cell state distribution shifts induced by signal combinations, and indicate a circuit model for the probabilistic fate specification by a differentiation switch with controlled transcriptional heterogeneity. Noise levels drive the system from highly plastic to committed states, allowing the relative level of signal inputs to shift population structures. The model further predicts an early bipotent state expressing lineage-specifying factors of both fates, which we verify in our single-cell profiling experiment and a mouse embryonic visual cortex development dataset. Our work identifies a design principle of noise-driven additive regulation in the logarithmic cell-fate probability space, providing a new strategy for population-level stem cell control.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13622004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121748","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}
引用次数: 0
The C. elegans gustatory receptor homolog LITE-1 is a chemoreceptor required for diacetyl avoidance. 秀丽隐杆线虫的味觉受体同源物LITE-1是避免双乙酰所需的化学受体。
bioRxiv : the preprint server for biology Pub Date : 2026-10-06 DOI: 10.1101/2025.04.20.649642
Alan Koh, Eduard Bokman, Alexey Gavrikov, Javier Rodriguez, Changchun Chen, Alon Zaslaver, André Ex Brown
{"title":"The <i>C. elegans</i> gustatory receptor homolog LITE-1 is a chemoreceptor required for diacetyl avoidance.","authors":"Alan Koh, Eduard Bokman, Alexey Gavrikov, Javier Rodriguez, Changchun Chen, Alon Zaslaver, André Ex Brown","doi":"10.1101/2025.04.20.649642","DOIUrl":"10.1101/2025.04.20.649642","url":null,"abstract":"<p><p>The nematode <i>C. elegans</i> does not have eyes but can respond to aversive UV and blue light stimulation and even distinguish colours. The gustatory receptor homolog LITE-1 was identified in forward genetic screens for worms that failed to respond to blue light stimulation. When LITE-1 is expressed in body-wall muscles, it causes contraction in response to blue light suggesting that LITE-1 is both necessary and sufficient for blue light response. Here we show that in addition to light avoidance, LITE-1 is also required for worms' avoidance of high concentrations of diacetyl, an odorant that is attractive at low concentrations. Like blue light, diacetyl causes muscle contraction in transgenic worms engineered to express LITE-1 in body-wall muscles. These data are consistent with a direct chemoreceptor function for LITE-1 which would make it a multimodal sensor of aversive stimuli.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13419714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148650501","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}
引用次数: 0
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