Biology subjects

Ma, A.

Publications and source records attributed to Ma, A..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

The Speed Limit of Visual Perception: Bidirectional influence of image memorability and processing speed on perceived duration and memory recall

Visual stimuli are known to vary in their perceived duration, with some stimuli engendering so-called "time dilation" and others "time compression" effects. Previous theories have suggested these effects rely on the level of attention devoted to stimuli, magnitude of the stimulus dimension, or intensity of the population neural response, yet cannot account for the full range of experimental effects. Recently, we demonstrated that perceived time is affected by the image properties of scene clutter, size, and memorability (Ma, et al. 2024), with the former compressing and latter two dilating duration. Further, perceived duration also predicted recall of images 24h later, on top of memorability. To explain the memorability effect, we found that a recurrent convolutional neural network (rCNN) could recapitulate the time dilation effect by indexing the rate of entropy collapse, or "speed", across successive timesteps, with more memorable stimuli associated with faster speeds. Here, we replicate and extend these findings via three experiments (n=20ea.) where subjects performed a sub-second temporal bisection task using memorability stimuli with increasing memorability, but a constant speed (exp 1), increasing speed, but constant memorability (exp 2), or increasing in both (exp 3), each followed by a surprise memory test 24hr later. We found that either increasing memorability or speed alone led to time dilation effects, with faster/slower speeds shifting memory recall by [~]8.4% in either direction. However, when both metrics increased, memorability dilated time while speed compressed it, while still improving recall overall. These findings can be explained by a model wherein the visual system is tuned to a preferred speed for processing stimuli that scales with the magnitude of visual response, such that stimuli closer to this speed are dilated in time. Overall, these findings provide a new lens for interpreting time dilation/compression effects and how visual stimuli are prioritized at temporal scales. Author SummaryRecent work has demonstrated a link between perceived duration and memory recall, with memorable images dilating time, and perceived duration in turn affecting memory. The link between these two can be indexed by the speed at which images are processed in recurrent convolutional neural networks, yet the limits of this link remain untested. Here, we tested three groups on a timing task using three sets of stimuli selected according to both their memorability and speed. We find that when one factor is held constant, both memorability and speed still dilate perceived duration, with speed alone accounting for a shift in memory recall of [~]17%. However, when speeds are raised to their highest limits, perceived duration is instead compressed. An inverted-U shape rule between time dilation and compression over speed that is moderated by memorability explains this effect and suggests the visual system shifts between these modes to both gather more information and conserve energy, respectively.

neuroscience↗

bioRxiv2025

An Intrinsic-hoc Framework for Heterogeneous Cellular Senescence Elucidation Using Deep Graph Representation Learning and Experimental Validation

Cellular senescence is a primordial driver of tissue and organ aging, and the accumulation of senescent cells (SnCs) has been implicated in numerous age-related diseases. A major barrier to studying senescence is the rarity and heterogeneity of SnCs, which are not a uniform population but instead comprise diverse senotypes shaped by cell-of-origin and microenvironmental context. Such heterogeneity exceeds what classical senescence hallmarks can resolve at single-cell resolution, motivating the need for computational frameworks that can capture senotype-level diversity intrinsically. Here, we introduce DeepSAS, a deep graph representation learning framework that robustly identifies cell-type-specific SnCs and their senescence-associated genes (SnGs). DeepSAS incorporates a heterogeneous graph that integrates intracellular transcriptional states with intercellular communication cues, enabling the joint inference of senescent cells and senescence-linked genes through attention-based contrastive learning. Applied to public healthy eye and lung atlases, DeepSAS identified SnCs whose proportions positively correlate with aging. From in-house idiopathic pulmonary fibrosis (IPF) patient scRNA-seq data, DeepSAS detected 1,678 SnCs (out of 24,125 cells) and 263 SnGs across 26 cell types, including 43 SnGs that are uniquely associated with a single cell type. We generated high-resolution Xenium spatial transcriptomics data to further validate SnGs in IPF, revealing NFE2L2 as a SnG specifically enriched in CTHRC1+ fibroblasts. Notably, the ex vivo bleomycin-induced senescence in human precision-cut lung slice (hPCLS) samples similarly identified NFE2L2 as an SnG in CTHRC1+ fibroblasts, albeit with stronger transcriptional signals, suggesting mechanistic differences in senescence cells associated with chronic and acute injury. Overall, DeepSAS uncovers distinct senescence programs and infers cell-type-specific SnGs that are difficult to resolve using existing marker-based approaches. We believe it offers a generalizable and translationally relevant strategy for advancing senescence biology and therapeutic development.

bioinformatics↗

bioRxiv2025

Harnessing the Power of Single-Cell Large Language Models with Parameter Efficient Fine-Tuning using scPEFT

Single-cell large language models (scLLMs) capture essential biological insights from vast single-cell atlases but struggle in out-of-context applications, where zero-shot predictions can be unreliable. To address this, we introduce a single-cell parameter-efficient fine-tuning (scPEFT) framework that integrates learnable, low-dimensional adapters into scLLMs. By freezing the backbone model and updating only the adapter parameters, scPEFT efficiently adapts to specific tasks using limited custom data. This approach mitigates catastrophic forgetting, reduces parameter tuning by over 96%, and decreases GPU memory usage by more than half, significantly enhancing scLLMss accessibility for resource-constrained researchers. Validated across diverse datasets, scPEFT outperformed zero-shot models and traditional fine-tuning in disease-specific, cross-species, and under-characterized cell population tasks. Its attention-mechanism analysis identified COVID-related genes associated with specific cell states and uncovered unique blood cell subpopulations, demonstrating scPEFTs capacity for condition-specific interpretations. These findings position scPEFT as an efficient solution for improving scLLMs utilities in general single-cell analyses.

cell biology↗

bioRxiv2025

Female-biased vascular smooth muscle cell gene regulatory networks predict MYH9 as a key regulator of fibrous plaque phenotype

Atherosclerosis, a chronic inflammatory condition driving coronary artery disease (CAD), manifests in two primary plaque types: unstable atheromatous plaques and stable fibrous plaques. While significant research has focused on atheromatous plaques, recent studies emphasize the growing importance of fibrous plaques, particularly in females under 50 years of age, where erosion on fibrous plaques significantly contributes to coronary thrombosis. The molecular mechanisms underlying sex differences in atherosclerotic plaque characteristics, including vascular smooth muscle cell (VSMC) contributions, remain understudied. Therefore, we utilized sex-specific gene regulatory networks (GRNs) derived from VSMC gene expression data from 119 male and 32 female heart transplant donors to identify molecular drivers of fibrous plaques. GRN analysis revealed two female-biased networks in VSMC, GRNfloralwhite and GRNyellowgreen, enriched for inflammatory signaling and actin remodeling pathways, respectively. Single-cell RNA sequencing of carotid plaques from female and male patients confirmed the sex specificity of these networks in VSMCs. Further sub cellular phenotyping of the single-cell RNA sequencing revealed a sex-specific gene expression signature within GRNyellowgreen for VSMCs enriched for contractile and vasculature development pathways. Bayesian network modeling of the GRNyellowgreen identified MYH9 as a key driver gene. Indeed, elevated MYH9 protein expression in atherosclerotic plaques was associated with higher smooth muscle cell content and lower lipid content in female plaques, suggesting its involvement in fibrous plaque formation. Further proteomic analysis confirmed MYH9s upregulation in female fibrous plaques only and its correlation with stable plaque features. These findings provide novel insights into sex-specific molecular mechanisms regulating fibrous plaque formation.

genomics↗

bioRxiv2025

Epigenetic Modulation, Intra-tumoral Microbiome and Immunity in Early Onset Colorectal Cancer

BackgroundThe incidence of colorectal cancer (CRC) in young adults (age of diagnosis < 50 years old) has been rapidly increasing. Although [~]20% of early-onset (EO) CRC cases are due to germline mutations, the etiology of the majority of EOCRC cases remains poorly understood. Non-genetic factors such as environmental exposure and lifestyle changes are likely to have a direct link to the increased incidence of sporadic EOCRC. We hypothesize that such factors may be observable as differences in the EOCRC epigenome, microbiome and immunome. We sought to address this by comparing differences in DNA methylation from the cohort of colorectal cancer patients in The Cancer Genome Atlas (TCGA). Further, we carefully identified intra-tumoral microbes from TCGA and two other datasets and then related the microbes to EOCRC status and deconvolved immune cell abundances. We found that DNA methylation (DNAm) age acceleration by12 years when compared with average-onset CRC (AOCRC) patients. Differentially methylated sites associated with genes are related to CREB signaling in neurons, G protein coupled receptor signaling, phagosome formation and S100 family signaling. These differences were validated in the gene expression from TCGA and a second, larger real-world dataset from the Oncology Research Information Exchange Network (ORIEN). However, no consistent differences were observed in the intra-tumor microbes between EOCRC and AOCRC. Interestingly, the most abundant microbes interacted with the immune systems differently between the EOCRC and AOCRC tumors, characterized by more, larger, positive correlations in EOCRC. These data suggest epigenetic modulation and accelerated aging may play a key role in the development of EOCRC. SIGNIFICANCEWe investigated whether environmentally driven factors contribute to early-onset colorectal cancer (EOCRC). We observed accelerated epigenetic aging in EOCRC and epigenetic changes associated with chronic inflammation. Tumor immune cell abundances correlated more strongly with microbes in EOCRC than average-onset CRC. These data suggest a dysregulation of immune response in EOCRC, driving chronic inflammation and tissue aging.

cancer biology↗

bioRxiv2025

Analysis of Head and Neck Cancer scRNA-seq Data Identified PRDM6 Promotes Tumor Progression by Modulating Immune Gene Expression

Head and neck squamous cell carcinoma (HNSCC) is a biologically aggressive and heterogeneous group of cancers with limited treatment options for patients who do not respond to standard therapies. While HPV-related HNSCCs tend to show better therapeutic outcomes, we still had limited understanding of the immune mechanisms underlying these cancers. Immune-responsive genes (IRGs) have emerged as critical factors in regulating both tumor progression and immune response. Recent advances in single-cell RNA sequencing (scRNA-seq) and the development of cell-type specific regulon inference tools, such as IRIS3, have provided new insights into the tumor immune microenvironment. In this study, we leveraged the IRIS3 platform to analyze scRNA-seq data from HNSCC patient samples, identifying novel transcription factor (TF)-IRG networks that contribute to tumor proliferation and immune escape. Specifically, we identified PRDM6, a histone methyltransferase, possesses the previously unknown role in promoting tumor cell proliferation by inducing IRG expression. We further demonstrated that HPV viral oncoproteins (E6/E7) oncoproteins up-regulate the PRDM6 expression, which associates PRDM6 with HPV-positive HNSCC.

cancer biology↗

bioRxiv2025

Effects of Lamina-Chromatin Attachment on Super Long-Range Chromatin Interactions

The interactions between chromatin and lamin proteins localized on the nuclear envelope play a crucial role in the three-dimensional (3D) organization of the genome. This study investigates the influence of lamin associated domains (LADs) on genome organization at the chromosome level using 3D polymer models of mouse embryonic fibroblasts (MEFs) and embryonic stem cells (mESCs). By integrating genome-wide LAD maps from DamID assays, we simulated chromatin conformations with and without LAD attachment to the nuclear envelope. Our results show that incorporating LAD-lamin interactions yields a radial chromatin distribution consistent with experimental observations. Moreover, LAD-lamin interactions induce significant super long-range chromatin contacts across distant genomic regions. These findings suggest two distinct mechanisms driving induction of chromatin interactions by LAD-lamin attachment.

genomics↗

bioRxiv2025

GEI-17-Mediated SUMOylation of GDI-1 Regulates Apoptotic Cell Clearance

Apoptotic cell clearance represents the final stage of apoptosis, and involves phagosome formation, maturation, and digestion. Here, we found that SUMO modifications participate in apoptotic cell clearance by influencing phagosomal degradation activity in C. elegans. The SUMO E3 ligase, GEI-17, SUMOylates GDP dissociation inhibitor (GDI-1) at K270 to trigger phagosomal degradation. Upon SUMOylation, GDI-1 facilitates release of GDP-bound RAB-1, which is subsequently converted to the GTP-bound form in a manner dependent on GDI displacement factor, PRAF-3. RAB-1 conversion enables binding and translocation of RAB-7 from the endoplasmic reticulum to Golgi to promote phagosome maturation and degradation activity. In the absence of GDI-1 SUMOylation, GDI-1 binds to GDP-RAB-1, sequestering it in the cytoplasm, resulting in impaired phagosomal degradation. Furthermore, we found SUMOylation of GDI1 at a conserved site plays a crucial role in efferocytosis regulation in mammals. This study defines a previously unrecognized mechanism by which SUMOylation drives apoptotic cell clearance.

cell biology↗

bioRxiv2025

A20's Linear Ubiquitin Binding Motif Restrains Pathogenic Activation of TH17/22 cells and IL-22 Driven Enteritis

A20, encoded by the TNFAIP3 gene, is a protein linked to Crohns disease and celiac disease in humans. We now find that mice expressing point mutations in A20s M1 ubiquitin binding motif (ZF7) spontaneously develop proximate enteritis that requires both luminal microbes and T cells. Cellular and transcriptomic profiling reveal expansion of TH17/22 cells and aberrant expression of IL-17A and IL-22 in intestinal lamina propria of A20ZF7 mice. While deletion of IL-17A from A20ZF7/ZF7 mice exacerbates enteritis, deletion of IL-22 abrogates intestinal epithelial cell hyperproliferation, barrier dysfunction, and alarmin expression. A20ZF7/ZF7 TH17/22 cells autonomously express more ROR{psi}t and IL-22 after differentiation in vitro. ATAC sequencing identified an enhancer region upstream of the Il22 gene in A20ZF7/ZF7 T cells, and this enhancer demonstrated increased activating histone acetylation coupled with exaggerated Il22 transcription. Finally, CRISPR/Cas9-mediated ablation of A20ZF7 in human T cells increases ROR{psi}t expression and IL22 transcription. These studies link A20s M1 ubiquitin binding function with ROR{psi}t expression, epigenetic activation of TH17/22 cells, and IL-22 driven enteritis.

immunology↗

bioRxiv2024

TrimNN: Characterizing cellular community motifs for studying multicellular topological organization in complex tissues

The spatial organization of cells plays a pivotal role in shaping tissue functions and phenotypes in various biological systems and diseased microenvironments. However, the topological principles governing interactions among cell types within spatial patterns remain poorly understood. Here, we present the Triangulation Cellular Community Motif Neural Network (TrimNN), a graph-based deep learning framework designed to identify conserved spatial cell organization patterns, termed Cellular Community (CC) motifs, from spatial transcriptomics and proteomics data. TrimNN employs a semi-divide-and-conquer approach to efficiently detect over-represented topological motifs of varying sizes in a triangulated space. By uncovering CC motifs, TrimNN reveals key associations between spatially distributed cell-type patterns and diverse phenotypes. These insights provide a foundation for understanding biological and disease mechanisms and offer potential biomarkers for diagnosis and therapeutic interventions.

bioinformatics↗

bioRxiv2024

Drip irrigation suppresses methane emissions by reshaping the rhizosphere microbiomes in rice

The rhizosphere microbiomes of rice plants under conventional flood irrigation consist of highly complex consortia of microorganisms and in particular methanogens purportedly associated with methane emissions therein. Controlled irrigation has been proposed as a cultivation method of choice over continuous flooding to reduce water and fertilizer usage in an aerobic environment. However, a systemic understanding of the assembly and function of microbiota in the rhizosphere under drip and flood irrigation remains unclear. Using empirical analyses, we report a significant reduction in methane emissions in controlled irrigation compared to the flooded environment. Genotypic or varietal differences did not influence such methane emissions under conventional flooded cultivation of rice. Using metagenomic sequencing and computational analyses, we provide a deeper understanding of how drip irrigation or continuous flooding affect the root-associated microbiomes in rice. Rhizosphere soil from two different rice varieties, Huanghuazhan and Temasek rice, grown under drip or flood conditions in a greenhouse was collected over 2 months post-transplantation for metagenomic analysis. Our results reveal that drip irrigation favours microbes involved in the nitrifying-denitrifying processes while continuous flooding enriches for methanotrophs and methanogenic archaea. Syntrophic microbiomes associated with methanogenesis were significantly reduced in drip irrigation. Several keystone taxa were evident in the co-occurrence network model related to methanogenic, methanotrophic, nitrifying, sulphur-oxidising and sulphur-reducing activities. Lastly, oxygen availability and redox potential were identified as key drivers that reshape rhizosphere microbiota and the associated metabolic functional differences observed between the two irrigation regimes leading up to the microbial mitigation of climate impact. IMPORTANCEUnlike previous studies in alternate wet-dry irrigation systems, this study characterised the rice microbiomes in a controlled drip irrigation settings where water levels were maintained at low levels and soil remained unflooded throughout the entire season in a greenhouse. A reduction of more than 90% in methane emissions was observed with drip irrigation compared to flood irrigation. Significant correlation was found between levels of methane emitted and mcrA gene copies detected with a Pearson correlation coefficient R of 0.77 and p-value of 2.3e-10. Methanogens are highly abundant in continuous flooded rice soil and are significantly reduced in drip-irrigated soil. Metagenomic profiling indicates that the shifts in microbial diversity under drip irrigation favour nitrifying microorganisms and is likely influenced by increased oxygen availability due to higher soil redox potential.

microbiology↗

bioRxiv2024

Resolving an unconventional non-photochemical quenching signature at the light-to-dark transition

Non-photochemical quenching (NPQ) protects photosynthetic organisms via diverse molecular players contributing at varying timescales. However, in the absence of one of the largest contributors to NPQ, energy-dependent quenching (qE), we observe an unusual but universal phenomenon: a transient increase in quenching in the dark following high light exposure. To mechanistically interrogate this light-to-dark (LtD) NPQ phenotype, we performed chlorophyll fluorescence lifetime snapshot measurements across a diverse array of Arabidopsis mutant backgrounds and chemical treatments. We found that the electrochemical gradient across the thylakoid membrane is essential for this phenomenon. Through analysis of higher-order Arabidopsis mutants, we also found that LtD NPQ is independent of the known forms of photoprotective NPQ, as well as the major and minor light-harvesting complexes (LHCII). Our results point to LtD NPQ as a photoinhibition (qI)-related, reaction center quenching with implications for photoprotection in fluctuating light.

plant biology↗

bioRxiv2024

scGNN+: Adapting ChatGPT for Seamless Tutorial and Code Optimization

Foundation models have transformed AI by leveraging large-scale data to efficiently perform diverse tasks, and their applications in bioinformatics are primarily focused on data-centric tasks like cell type annotation and gene expression analysis. However, their potential extends beyond data analysis, offering significant opportunities in software development and optimization, such as code refinement, tutorial generation, and advanced visualization. For example, models like OpenAI Codex can suggest optimized code snippets and generate well-documented, reproducible workflows, enhancing accessibility and reducing computational complexity. Despite these advantages, the use of foundation models for improving computational tool engineering in single-cell research remains underutilized. To address this gap, we developed scGNN+, a web-based platform that combines the power of graph neural networks with the capabilities of ChatGPT to enhance reproducibility, code optimization, and visualization. scGNN+ further simplifies the process for users by generating standardized, well-annotated code, making complex procedures more accessible to non-programmers. Additionally, ChatGPT integration allows users to create high-quality, customizable visualizations through natural language prompts, improving data interpretation and presentation. Ultimately, scGNN+ offers a user-friendly, reproducible, and optimized solution for single-cell research, leveraging the full potential of foundation models in bioinformatics. scGNN+ is publicly available at https://bmblx.bmi.osumc.edu/scgnn+.

bioinformatics↗

bioRxiv2024

In vivo analysis of the relationship between CP26 and qE-type NPQ via higher-order Arabidopsis cp26 mutants

CP26 is a monomeric minor light-harvesting complex of PSII (LHCII) protein that connects major LHCII trimers to the PSII core in photosynthetic thylakoid membranes. Previous studies have proposed that CP26 is not only involved in light harvesting but could also be involved in non-photochemical quenching (NPQ). Here, we analyzed higher-order Arabidopsis cp26 mutants using biophysical and pharmacological approaches to investigate the nature of NPQ and its relationship to known NPQ regulators (PSII subunit S (PsbS), the xanthophyll-converting enzyme VDE and the pH gradient across the thylakoid membrane). Maximum PSII quantum efficiencies (Fv/Fm) and chlorophyll fluorescence lifetimes in the dark were significantly lower in cp26 mutants, confirming that CP26 deficiency leads to a sustained quenched state even in the absence of light. Destabilized PSII-LHCII supercomplexes as observed with native PAGE analysis are the likely cause for this pre-quenched state, without other antenna proteins being able to rescue this phenotype. Further analyses revealed that cp26 mutants exhibit modest (single mutant) to highly significant (double mutants) reductions in overall NPQ capacity, which do not directly rely on PsbS and VDE (although the effect is more pronounced when these qE components are altered) but depend on thylakoid lumen acidification and protonation of protein residues. Together, these results show that the NPQ component lacking in cp26 mutants acts independently of qE and qZ and is induced in a slower phase of NPQ induction that most likely relies on pH-dependent conformational changes.

plant biology↗

bioRxiv2024

CD28 Shapes T Cell Receptor Signaling by Regulating ZAP70 Activation and Lck Dynamics

T cell activation requires T cell receptor (TCR) engagement, which initiates a series of proximal events including tyrosine phosphorylation of the CD3 and TCR{zeta} chains, recruitment, and activation of the protein tyrosine kinases Lck and ZAP70, followed by recruitment of adapter and signaling proteins. CD28 co-stimulation is also required to generate a functional immune response. Currently we lack a full understanding of the molecular mechanism of CD28 activation. TCR microclusters (MC) are submicron-sized molecular condensates and basic signaling units that form immediately after TCR ligation. Our results show that CD28 co-stimulation specifically accelerated recruitment of ZAP70 to the TCR{zeta} chain in MCs and increased ZAP70 activation. This CD28-mediated acceleration of ZAP70 recruitment was driven by enhanced Lck recruitment to the MCs. A greater spatial separation between active and inactive species of Lck was also observed in the MCs as a consequence of CD28 co-stimulation. These results suggest that CD28 co-stimulation may lower the TCR activation threshold by enhancing the activated form of Lck in the TCR MCs.

immunology↗

bioRxiv2024

Deficiency in a special dynein DNAH12 causes male infertility by impairing DNAH1 and DNALI1 recruitment in humans and mice

Asthenoteratozoospermia, a prevalent cause of male infertility, lacks a well-defined etiology. DNAH12 is a special dynein featured by the absence of a microtubule-binding domain, however, its functions in spermatogenesis remain largely unknown. Through comprehensive genetic analyses involving whole-exome sequencing and subsequent Sanger sequencing on infertile patients and fertile controls from six distinct families, we unveiled six biallelic mutations in DNAH12 that co-segregate recessively with male infertility in the studied families. Transmission electron microscopy (TEM) revealed pronounced axonemal abnormalities, including inner dynein arms (IDAs) impairment and central pair (CP) loss in sperm flagella of the patients. Mouse models (Dnah12-/- and Dnah12mut/mut) were generated and recapitulated the reproductive defects in the patients. Noteworthy, DNAH12 deficiency did not show effects on cilium organization and function. Mechanistically, DNAH12 was confirmed to interact with two other IDA components DNALI1 and DNAH1, while disruption of DNAH12 leads to failed recruitment of DNALI1 and DNAH1 to IDAs and compromised sperm development. Furthermore, DNAH12 also interacts with radial spoke head proteins RSPH1, RSPH9, and DNAJB13 to regulate CP stability. Moreover, the infertility of Dnah12-/- mice could be overcome by intracytoplasmic sperm injection (ICSI) treatment. Collectively, DNAH12 plays a crucial role in the proper organization of axoneme in sperm flagella, but not cilia, by recruiting DNAH1 and DNALI1 in both humans and mice. These findings expand our comprehension of dynein component assembly in flagella and cilia and provide a valuable marker for genetic counseling and diagnosis of asthenoteratozoospermia in clinical practice.

genetics↗

bioRxiv2024

Loss-of-function of ALDH3B2 transdifferentiates human pancreatic duct cells into beta-like cells

Replenishment of pancreatic beta cells is a key to the cure for diabetes. Beta cells regeneration is achieved predominantly by self-replication especially in rodents, but it was also shown that pancreatic duct cells can transdifferentiate into beta cells. How pancreatic duct cells undergo transdifferentiated and whether we could manipulate the transdifferentiation to replenish beta cell mass is not well understood. Using a genome-wide CRISPR screen, we discovered that loss-of-function of ALDH3B2 is sufficient to transdifferentiate human pancreatic duct cells into functional beta-like cells. The transdifferentiated cells have significant increase in beta cell marker genes expression, secrete insulin in response to glucose, and reduce blood glucose when transplanted into diabetic mice. Our study identifies a novel gene that could potentially be targeted in human pancreatic duct cells to replenish beta cell mass for diabetes therapy.

genetics↗

bioRxiv2024

Regulation of Chromatin Modifications through Coordination of Nucleus Size and Epithelial Cell Morphology Heterogeneity

Cell morphology heterogeneity is pervasive in epithelial collectives, yet the underlying mechanisms driving such heterogeneity and its consequential biological ramifications remain elusive. Here, we observed a consistent correlation between the epithelial cell morphology and nucleus morphology during crowding, revealing a persistent log-normal probability distribution characterizing both cell and nucleus areas across diverse epithelial model systems. We further showed that this morphological diversity arises from asymmetric partitioning during cell division. Moreover, we provide insights into the impact of nucleus morphology on chromatin modifications. We demonstrated that constraining nucleus leads to downregulation of the euchromatic mark H3K9ac and upregulation of the heterochromatic mark H3K27me3. Furthermore, we showed that nucleus size regulates H3K27me3 levels through histone demethylase UTX. These findings highlight the significance of cell morphology heterogeneity as a driver of chromatin state diversity, shaping functional variability within epithelial tissues.

biophysics↗