Biology subjects

Wang, N.

Publications and source records attributed to Wang, N..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

LTBP isoforms differentially encode TGF-β spatial localization and activation

TGF-{beta} signals through a conserved pathway yet produces diverse outcomes, pointing to regulatory mechanisms upstream of receptor engagement. A family of four latent TGF-{beta} binding proteins (LTBPs) tether pro-TGF-{beta}s and control their localization and activation, but how distinct LTBPs contribute to this regulation is unclear. Here we combine cryo-electron microscopy with functional assays to dissect LTBP-pro-TGF-{beta} interactions. We resolve the LTBP-1/pro-TGF-{beta}1 and LTBP-3/pro-TGF-{beta}3 complex structures, revealing a conserved yet plastic hydrophobic binding interface, and systematically map key residues across all four LTBP and three pro-TGF-{beta} subtypes that determine binding specificity and affinity. Unexpectedly, LTBP-2, previously thought incapable of TGF-{beta} binding, engages pro-TGF-{beta}1 through a covalent linkage via its 16th EGF-like domain, providing a mechanistic link between LTBP-2 function and TGF-{beta} signaling. Beyond tethering, LTBP-3 shifts pro-TGF-{beta}3 from spontaneous activation toward integrin dependence, establishing LTPBs as dynamic modulators that dictate not only where but also how TGF-{beta} is unleashed. Collectively, these findings establish that LTBPs are not redundant ECM scaffolds but a family of functionally distinct regulators that differentially encode TGF-{beta} spatial localization and activation, with implications for isoform-selective therapeutic strategies.

biochemistry↗

bioRxiv2026

Field-Correcting GRAPPA (FCG): a technique to correctspatiotemporal-varying phase errors in Echo Planar Imaging

PurposeTo develop a Field-Correcting GRAPPA (FCG) technique to correct the spatiotemporal-varying phase errors in EPI caused by eddy currents. MethodsThe fast-changing gradient in EPI causes strong eddy current effects and associated spatiotemporal-varying phase errors, producing significant image artifacts. The use of higher gradient amplitude, slew rate, and ramp sampling factor for faster imaging exacerbates this problem. In this work, FCG was developed to address this challenge by using a multi-layer perceptron (MLP) to provide a compact representation of a family of GRAPPA-like kernels that correct the spatiotemporal-varying phase errors in the data. A dedicated calibration pipeline was designed to acquire high-quality source and target data for MLP training in both slice-by-slice and simultaneous multi-slice (SMS) acquisitions. To validate FCGs assumptions and performance, a field camera was used to provide ground-truth measurement of phase patterns. The performance of FCG was further validated on phantom and in vivo experiments using demanding EPI trajectories across multiple 3T and 7T systems. ResultsField camera measurements revealed strong spatiotemporal phase variations along the kx direction that repeat along ky during EPI readouts. The experiments on high-performance systems across 3T and 7T demonstrate that FCG can provide superior correction for the artifacts induced by spatiotemporal-varying phase errors compared with existing approaches. ConclusionFCG is an effective and robust method for correcting spatiotemporal phase errors in EPI, enabling improved image quality on high-performance systems.

bioengineering↗

bioRxiv2026

Temporal dynamics and functional divergence of the chloroplast division apparatus in Oryza sativa

O_LIChloroplast division is governed by a conserved protein machinery, yet empirical characterization of these regulators remains limited in rice, a primary target for C4 engineering. Increased chloroplast occupancy in bundle sheath cells is a hallmark of the C4 pathway and so manipulating division is a potential strategy to achieve this goal. C_LIO_LIThrough developmental transcript profiling and image analysis, we identified a discrete window of active chloroplast proliferation in rice leaves, coinciding with peak expression of conserved plastid division genes. Functional characterization via overexpression revealed regulatory behaviours distinct from those in Arabidopsis thaliana. Overexpression of OsFtsZ1&2 resulted in fewer, enlarged chloroplasts per bundle sheath cell, whereas OsMCD1&OsMinE restricted plastid expansion without altering division rates. Conversely, overexpressing OsPDV1&2 or OsARC6&OsDRP5B increased plastid size without affecting total count. When OsPDV1&2 were co-expressed with transcriptional regulator ZmG2, we observed modest increases in chloroplast size alongside reduced stomatal aperture, increased stomatal density, and higher intrinsic water-use efficiency. C_LIO_LIThe results define the temporal landscape of plastid biogenesis in rice and demonstrate divergence across lineages. Our findings suggest that manipulating the division apparatus is insufficient to drive C4-like chloroplast biogenesis in the rice bundle sheath, highlighting the complexity of plastid-host cell coordination in cereals. C_LI

Plant Biology↗

bioRxiv2026

3D Passive Cavitation Mapping (3D-PCM) with a Large-aperture Planar Array

Urinary stone disease is a common urological condition with increasing incidence, particularly in developed countries. Laser lithotripsy (LL) has become a preferred minimally invasive treatment due to its high precision and low tissue damage. Recent studies suggest that cavitation plays a critical role in stone damage during LL, and three-dimensional passive cavitation mapping (3D-PCM) has emerged as a promising tool for detecting these events. However, clinical translation of 3D-PCM remains challenging due to limitations in imaging depth, field of view (FOV), and procedural compatibility. Here, we present a large-FOV dual-modality imaging system (3D-PCM and B-mode ultrasound) based on a large-aperture planar ultrasound array. Through array optimization and model-based reconstruction, our system achieves an expanded FOV of [~]40 x 40 mm2 at a clinically relevant imaging depth of [~]110 mm, while maintaining high spatial resolution of [~]0.6 mm laterally and [~]0.4 mm axially. In vivo experiments in a porcine model demonstrate that the reconstructed cavitation distribution correlates well with stone damage. Our technology has the potential to provide real-time treatment feedback during LL without disrupting the standard workflow.

bioengineering↗

bioRxiv2026

Decoding Spatial Programs in Human Glioblastoma Through Surprisal Information-Theoretical Analysis

Glioblastoma (GBM) is a highly heterogeneous and invasive brain tumor in which complex interactions among tumor cells, immune cells, and neurons shape disease progression and therapeutic resistance. Resolving spatial patterns programs in glioblastoma (GBM) requires analytical approaches that go beyond variance-driven embeddings. Here, we applied thermodynamic surprisal analysis, an information-theoretic decomposition framework, to spatial transcriptomic sequencing from human GBM specimens to identify orthogonal constraint modes that capture dominant and previously hidden spatial programs. Surprisal analysis revealed structured patterns in the data that are not highlighted by standard approaches such as PCA or cell type deconvolution, including immune-activation-associated signatures as well as spatial programs consistent with synapse remodeling. Coupling surprisal decomposition with spatial ligand-receptor interaction analysis, NICHES, along with multiplexed protein imaging connected these spatial hidden modes to reveal potential communication networks. Together, these results position surprisal analysis as a powerful, complementary strategy for interrogating spatial tumor architecture, enabling discovery of non-obvious spatial programs and interactions that are obscured by variance-based methods.

systems biology↗

bioRxiv2026

Phase-tuned interfacial condensates drive transcellular access

Nanocondensates occupy mesoscopic scale in both spatial scale and thermodynamic state, and the mesoscopic scale is central to structure-function conversion in living systems. However, how the dual mesoscopic properties of nanocondensates support biological function remains unclear because their small size and rapid dynamics hinder direct observation in living cells. Here we construct nanocondensates in situ at the cell-membrane interface and observe them permeating membranes within seconds, diffusing freely, exiting cells within minutes, re-entering neighbouring cells and traversing multilayered barriers. We report the first observation of this phenomenon and term it nanocondensate tunnelling. We find that nanocondensates cross membranes without membrane enclosure, preserving their wetting characteristics after passage. Theoretical and ultrastructural analyses support a transient-pore model linking this behaviour. We exploit nanocondensate tunnelling to transport small molecules, siRNA and antibodies across cellular barriers, and small molecules and siRNA across a multilayered corneal barrier, demonstrating its functional capacity for intercellular transfer. Our results suggest that nanocondensate tunnelling represents a previously undescribed mode of intercellular transfer. Nanocondensate tunnelling provides a physical basis for biologics delivery and a testable framework for investigating unresolved biological phenomena such as viral permeation.

bioengineering↗

bioRxiv2026

Q-DOAS: A Proximity Quenching Assay for Real-Time Detection of Early Protein Aggregation Events

Accurate measurement of protein aggregation is essential for studying neurodegenerative diseases. The standard ThT assay reports on amyloid formation but is blind to early oligomers and is prone to interference. We describe Q-DOAS, a plate-reader assay that quantifies protein self-assembly in real time via proximity-quenching of a single, site-specifically conjugated dye (BODIPY-TMR). Using mutant Huntingtin-exon 1 (mHTT-Ex1) and -Synuclein A53T, we show Q-DOAS detects pre-amyloid oligomers, yielding quantitative kinetic data compatible with mechanistic analysis. We demonstrate its utility to dissect mutational effects, screen for protein and small-molecule inhibitors, and quantify amyloid seeding activity in cellular and mouse models of Huntingtons disease. Q-DOAS also detects seeds in cerebrospinal fluid from Parkinsons disease patients without amplification. Q-DOAS provides a sensitive, robust, and scalable tool for studying the earliest events in amyloid pathologies and for advancing therapeutic development.

biochemistry↗

bioRxiv2026

Scout-based Multi-Echo NAvigator (SMENA) for high temporal resolution motion and B0 estimation and correction: applications to multi-echo GRE and EPTI

PurposeTo develop a data-driven technique, Scout-based Multi-Echo NAvigator (SMENA), for joint estimation of motion and B0 inhomogeneity ({delta}B0) at a temporal resolution of [~]200 ms with minimal additional scan time for gradient-echo acquisition. MethodsSMENA consists of two key acquisition components: SMENA-scout and SMENA-nav. SMENA-scout is a rapid 3D 4-mm multi-echo acquisition completed in less than 8 seconds, providing images with matched contrast and phase at multiple echo times. SMENA-nav captures signal variations induced by motion and{delta} B0 during the scan using compact multi-echo navigator trajectories (3.5 ms) embedded within each TR. Motion and{delta} B0 maps were jointly estimated every [~]200 ms through a model-based optimization framework relating SMENA-scout to SMENA-nav. The estimation accuracy and correction performance of SMENA were evaluated in simulations and in vivo using multi-echo GRE and GRE-EPTI acquisitions. Multiple prospective motion experiments, including large continuous movement and deep breathing, were investigated. ResultsIn both simulations and in vivo experiments, accurate motion and{delta} B0 estimation were achieved. Compared with motion-only estimation, joint estimation reduced rotation and translation errors. Joint motion and{delta} B0 correction resulted in substantial improvements in image quality, particularly at longer echo times, producing an NRMSE of 10.4% compared to 31.6% with motion-only correction. High-temporal-resolution tracking of motion and{delta} B0 enabled improved reconstruction quality in scenarios involving continuous motion and deep breathing. ConclusionSMENA enables high-temporal-resolution joint estimation of motion and{delta} B0 with minimal additional acquisition cost, providing a practical solution for motion- and{delta} B0-robust MRI.

neuroscience↗

bioRxiv2026

Enhanced Target Binding by Leritrelvir Restores Dimerization of Mpro Mutants and Mitigates Drug Resistance

The SARS-CoV-2 main protease (Mpro) has been a major target of antiviral drug development, leading to the development of inhibitors such as nirmatrelvir, the antiviral component of the COVID-19 drug Paxlovid. However, resistance-associated mutations that reduce the efficacy of current Mpro inhibitors, particularly nirmatrelvir, have emerged. Here, we evaluated the inhibitory activity of leritrelvir (RAY1216), an Mpro inhibitor approved in China for COVID-19 monotherapy, against a panel of Mpro variants carrying mutations at 12 resistance-associated residues distributed across four catalytic subsites. Using integrated biochemical, biophysical, structural, and cellular analyses, we demonstrate that leritrelvir retains stronger inhibitory activity against most tested resistant mutants compared with nirmatrelvir. Most of the tested mutations promote Mpro dimer dissociation, with E166V showing a particularly pronounced effect and markedly compromising nirmatrelvir binding. In contrast, thermal shift and size-exclusion chromatography assays demonstrate that leritrelvir binding restores dimerization of these Mpro mutants. Sixteen high-resolution crystal structures reveal that leritrelvir binding re-instates key dimer-interface interactions disrupted by resistance mutations. Mini-replicon assays further confirm leritrelvir to possess enhanced cellular antiviral efficacy compared with nirmatrelvir. Our findings indicate that tighter leritrelvir binding enables more effective inhibition of dissociation-prone Mpro mutants than nirmatrelvir, supporting its use as a more resilient antiviral agent for SARS-CoV-2 treatment.

molecular biology↗

bioRxiv2026

Integrating Histology with Spatial Molecular Programs Using a Multimodal Foundation Model

Histopathological assessment remains central to cancer diagnosis and stratification, yet its mechanistic interpretation remains limited without molecular context. To address this, we developed SQUALL, a multimodal foundation model integrating histology with spatial molecular programs. For pretraining, we assembled histMol, a large-scale corpus of 1.76 billion paired histology-spatial transcriptomics spots/bins across 33 tissues and 12 platforms from 3,446 tissue sections. Following pretraining, SQUALL enables transcriptome-wide virtual biomarker profiling, prognostically relevant spatial niches discovery, and integrative disease progression modeling. Leveraging its multimodal embeddings, SQUALL identifies niches associated with tertiary lymphoid structure (TLS) maturation and ovarian cancer relapse, reconstructs molecular trajectories of breast cancer invasion across 325,112 spots, and uncovers underlying transcriptional programs. Applied to whole-slide images from 898 patients, SQUALL outperforms existing pathology foundation models in outcome prediction while enabling interpretable risk stratification. Together, these results establish spatially aligned multimodal pretraining as a new paradigm for extending molecular insights into pathology images.

bioinformatics↗

bioRxiv2026

Characteristics of the C4 bundle sheath emerge in C3 rice after editing a plasma membrane proton ATPase

C4 photosynthesis improves light, water and nitrogen-use efficiencies and can raise yield by 50% compared with the ancestral C3 pathway. Engineering C4 traits into C3 crops could substantially boost food production but requires coordinated modifications to leaf anatomy and cell-specific photosynthetic function. For example, C4 leaves contain more numerous, shorter bundle sheath cells that are photosynthetically active. In searching for transcriptional regulators of bundle sheath development in C3 rice, we unexpectedly found OSA3, a plasma membrane H+-ATPase that is expressed in bundle sheath cells as they elongate, and when knocked out reduces their length due to reduced apoplastic acidification. Bundle sheath cell number and chloroplast occupancy are increased. Thus, switching between C3 and C4 bundle sheath identity is controlled by acid growth, and OSA3 represents a simple tool for C4 engineering.

plant biology↗

bioRxiv2026

Discovery of a CI-994 derivative as a dual modulator of class I HDACs and Wnt/β-catenin signaling for Alzheimer's disease therapy

Alzheimers disease (AD) is a multifactorial disease with mixed pathologies. Consequentially, drugs targeting multiple pathological processes may offer synergistic benefits. While histone deacetylase (HDAC) inhibitors have demonstrated efficacy in alleviating AD-related pathologies in animal models, the neuroprotective Wnt/{beta}-catenin signaling pathway remains compromised in AD brain. CI-994 is a class I HDAC inhibitor containing N-(2-aminophenyl)-benzamide. Our recent studies indicate that CI-994 is also an activator of Wnt/{beta}-catenin signaling by stabilizing Wnt co-receptor LRP6. We herein use CI-994 as a scaffold to develop novel potent dual modulators of class I HDACs and Wnt/{beta}-catenin signaling for AD therapy. Our lead compound, W2A-28, selectively inhibits class I HDAC1, 2 and 3 with IC50 values of 0.51 M, 0.68 M, and 0.22 M, respectively, and shows no inhibitory activities on other HDACs. Furthermore, W2A-28 potently activates Wnt reporter activity with an EC50 value of 1.61 M in Wnt-3A-expressing HEK293 cells. As expected, activation of Wnt/{beta}-catenin signaling by W2A-28 is associated with elevated LRP6 protein level. Importantly, W2A-28 displays excellent microsomal stability in both mouse and human liver microsomal stability assays, alongside high permeability and a lack of active efflux in MDR1-MDCKII models. Critically, W2A-28 treatment significantly enhances histone acetylation, activates Wnt/{beta}-catenin signaling, and suppresses tau phosphorylation in AD patient-specific cerebral organoids carrying APOE {varepsilon}4/{varepsilon}4 or APOE {varepsilon}3/{varepsilon}4 with PSEN1 M146V mutation. Our findings position W2A-28 as a promising multi-target drug candidate for AD therapy.

neuroscience↗

bioRxiv2026

3D-PAULM: Integrated Photoacoustic Tomography and Ultrasound Localization Microscopy for Multiparametric Brain and Tumor Imaging

Understanding processes such as blood-brain barrier (BBB) disruption and tumor progression can greatly benefit from simultaneous molecular, functional, and hemodynamic imaging in deep tissue, yet few existing imaging modalities can provide all three in a single system. Here, we present an integrated imaging platform that combines 3D photoacoustic tomography with ultrasound localization microscopy (3D-PAULM) to enable intrinsically co-registered, multiparametric imaging. 3D-PAULM unifies multispectral photoacoustic molecular imaging, ultrasound B-mode imaging, microbubble-enhanced power Doppler, and ultrasound localization microscopy, and concurrently measures blood oxygenation, blood perfusion, microvascular flow dynamics, and molecular probes from near-infrared dyes and photoswitchable phytochromes. We apply 3D-PAULM to quantify BBB leakage in focal ischemia and systemic inflammation, and to perform high-sensitivity molecular imaging of solid tumors alongside functional mapping of tumor hypoxia and super-resolved vascular remodeling. Together, these results establish 3D-PAULM as a versatile platform for integrated functional and molecular imaging in deep tissue.

bioengineering↗

bioRxiv2026

A unified population-genetic framework for inferring double reduction and higher-order two-locus linkage disequilibrium in autopolyploids

Polyploid genomes exhibit complex allelic interactions driven by polysomic inheritance that cannot be adequately captured by conventional pairwise linkage disequilibrium (LD) models, leaving higher-order dependency structures largely unresolved. Here, we develop a unified population-genetic framework that jointly infers double reduction and higher-order allelic associations in autopolyploids. By modeling dosage-dependent gametic structure, our approach reformulates LD as a hierarchical system, enabling decomposition of allelic dependencies beyond pairwise interactions. Through simulations, we show that conventional estimators systematically confound higher-order allelic structure with pairwise LD, leading to biased inference and loss of identifiability under dosage uncertainty. In contrast, our joint likelihood framework achieves asymptotically unbiased estimation and reveals that effective double reduction emerges as a composite parameter linking meiotic configuration to population-level allelic reshaping. Applying this model to Arabidopsis arenosa and cultivated potato, we uncover fundamental contrasts in genomic architecture. In natural populations, higher-order LD self-organizes into structured, long-range dependency networks, whereas predominantly clonal populations exhibit collapse of higher-order dependency structure. We further identify a spatial antagonism between double reduction and higher-order LD, demonstrating that elevated double reduction compresses the physical scale of allelic interactions. Our results demonstrate that autopolyploid genomes are organized as higher-order dependency systems rather than collections of pairwise associations, establishing higher-order allelic structure as a fundamental extension of classical LD theory.

genetics↗

bioRxiv2026

Multiphasic myelination and dendritic growth modulate qMRI signals in human visual cortex.

How does myelin develop in human visual cortex? By combining immunohistochemistry with in vivo and postmortem magnetic resonance imaging of longitudinal relaxation rate (R1), which increases with myelin content, we find that myelin and R1 increase across development but follow distinct trajectories. Immunohistochemistry reveals two phases of myelination: an infant phase of limited oligodendrogenesis, with myelin restricted to deep cortical layers, followed by widespread myelination across all layers during childhood. Cortical R1 also increases across development and correlates with myelin by childhood. However, in infancy, R1 increases outpace myelin growth and instead tracks dendritic arborization, indicating that the microstructural drivers of R1 change across development. We hypothesize that deep layer myelination in infancy contributes to early visual function whereas later myelination of superficial layers enables prolonged cortical plasticity and learning of complex visual behaviors.

neuroscience↗

bioRxiv2026

A Decade of Deep Learning-based Biomedical Image Segmentation

Biomedical image segmentation is a fundamental problem in computational biomedicine that aims to precisely delineate anatomical and biological structures, tissue types, or pathological regions in biomedical images. Accurate segmentation is essential for interpretation, decision-making, and quantitative analysis across a wide range of biological and medical applications. Over the past decade, the field has undergone a profound paradigm shift, evolving from task-specific specialist models to universal foundation models. This review provides an in-depth analysis of the evolution, tracing how the limitations of local discriminative learning drove the transition toward transformer-based global modeling, and large-scale generative pre-training. To help navigate the diverse landscape of interaction paradigms, we introduce the first systematic taxonomy of promptable biomedical image segmentation, categorizing existing methods into six distinct types, enabling users to intuitively select appropriate prompting strategies based on visual demonstrations and quickly pinpoint relevant literature (Prompt Type Visualization). Beyond model architectures, we discuss parallel advancements in dataset development, evaluation protocols, and application-specific adaptations across radiology, pathology, and biology. Integrating these powerful foundation models with rigorous domain-specific adaptation has great potential to improve patient outcomes and healthcare efficiency. Finally, we highlight key challenges in trustworthiness and clinical integration that must be overcome to realize the potential of the next generation of biological and medical generalists.

bioengineering↗

bioRxiv2026

Cas9/sgRNA-mediated genome editing of citrus via mature tissue transformation enables both high-efficacy genome editing and early flowering

CRISPR genome editing has shown tremendous potential in genetic improvement of citrus. So far, citrus genome editing has been conducted using juvenile tissues resulting in genome-edited citrus plants that require multiple years before they can produce flowers and fruit. Here we tested whether citrus genome editing via mature tissue transformation can overcome such a hurdle. CsLOB1 is a susceptibility gene for citrus canker caused by Xanthomonas citri subsp. citri (Xcc). The transcription activator-like effector PthA4 of Xcc activates CsLOB1 by binding to the effector-binding element in its promoter (EBEpthA4-CsLOBP). In Valencia sweet orange, two CsLOB1 promoter alleles are present: TI CsLOBP, and TII CsLOBP. We specifically utilized a CRISPR/Cas9 construct (GFP-p1380N-Cas9/sgRNA:CsLOBP2) targeting EBEpthA4 in TI CsLOBP but not TII CsLOBP to test genome editing efficacy and off-target mutations. GFP-p1380N-Cas9/sgRNA:CsLOBP2 function was first validated using Xcc-facilitated agroinfiltration in Valencia leaves. The construct was subsequently introduced into Valencia mature internodal stem segments via Agrobacterium-mediated transformation, generating three independent transgenic lines (#V2, #V3 and #V5). Targeted mutations in EBEpthA4-TI CsLOBP were detected in all three lines with mutation frequencies of 100%, 21.43% and 41.94% in #V2, #V3 and #V5, respectively, while no mutations were detected in TII CsLOBP. Infection with Xcc{Delta}pthA4:dCsLOB1.3, carrying a designer TALE that specifically activates TI CsLOBP, resulted in reduced canker symptoms in #V2. Importantly, all three EBEpthA4-TI CsLOBP edited lines flowered within 15 months. In sum, these results demonstrate that CRISPR/Cas9-mediated genome modification through mature citrus transformation can achieve high genome editing efficacy and overcome the juvenility.

plant biology↗

bioRxiv2026

MCT1 governs a metabolic checkpoint at pachytene during spermatogenesis

ABSTRACT/SUMMARYThe transition from mitosis to meiosis represents a fundamental cell-fate decision that requires coordinated remodeling of transcriptional and metabolic programs. While key transcriptional regulators of meiotic entry have been defined, how metabolic flux directly governs this process remains unclear. Here, we identify a monocarboxylate transporter1 (MCT1)-dependent metabolic checkpoint that controls meiotic progression in mammalian spermatogenesis. Through integrative single-cell transcriptomics, metabolic profiling, and computational perturbation modeling, we show that Stra8-driven meiotic initiation is coupled to a metabolic switch favoring monocarboxylic acid metabolism, prominently involving MCT1 (encoded by Slc16a1). Germ cell-specific deletion of Slc16a1 results in a complete arrest at the pachytene stage, characterized by defective homologous recombination, persistent DNA damage, and failure to activate the meiotic transcriptional program. Multi-omic analyses reveal that loss of MCT1 induces a metabolic stress-like state, suppresses expression of key meiotic regulators, and disrupts progression through the pachytene checkpoint. Mechanistically, we demonstrate that MCT1-mediated lactate influx drives histone H4 lysine 12 lactylation (H4K12la) at promoters of meiotic genes, thereby epigenetically licensing their expression. In the absence of MCT1, H4K12la deposition is lost at meiotic loci and redistributed toward stress-response pathways. Together, our findings suggest MCT1-mediated metabolism as an instructive signal that integrates metabolic state with epigenetic regulation to govern meiotic cell-fate progression, defining a previously unrecognized metabolic checkpoint at pachytene.

developmental biology↗