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Biology subjects

Yang, M.

Publications and source records attributed to Yang, M..

At least 109 records · Page 6Linked to original sources

A New Aneurysm Rupture-Prone Marfan Mouse Model with FBN1Q2467X Nonsense Mutation Reveals Adventitial Inflammation

Marfan syndrome (MFS) is a genetic disorder caused by mutations in fibrillin-1(FBN1), which encodes FBN1, a key structural component of the extracellular matrix. Mutations in FBN1 influence the severity of aortic disease and therapeutic responses, with aortic aneurysm being the leading cause of mortality in patients with MFS. To investigate the mechanisms driving aneurysm progression, we generated a mouse model (Fbn1Q2469X/+) carrying the FBN1Q2467X nonsense mutation identified in MFS patients. This mutation results in FBN1 deficiency. Although Fbn1Q2469X/+ mice appear normal, showing only mild, nonprogressive dilation of the aortic root and ascending aorta with minor reductions in blood pressure, homozygous Fbn1Q2469X/Q2469X mice develop spontaneous thoracic aortic aneurysms (TAA) that progress to rupture between 10 and 25 days of age, with 100% penetrance. Histopathology shows progressive vessel wall degeneration characterized by disorganized vascular smooth muscle cells, collagen loss, and elastic fiber fragmentation from early to late stages. RNA-seq analysis identifies inflammation as the dominant process in late-stage aneurysms. Immunofluorescence assay reveals inflammatory cells prominently localized to the adventitia near rupture sites, linking adventitial inflammation to aneurysm progression. This genetically modified Fbn1Q2469X/Q2469X mouse model consistently develops progressive aortic aneurysms and provides a reliable, cost-effective platform to investigate the molecular mechanisms of aneurysm progression and to evaluate therapeutic strategies in aneurysm diseases, including Marfan syndrome and related disorders.

genetics↗

Fast Hyperspectral and Super-Resolved Mapping of Lipid Membrane Polarity with Single-Molecule Sensitivity

Cell membranes display nanoscale heterogeneity in lipid composition and organization that regulates vital biological processes yet remains challenging to resolve with conventional imaging. We introduce spectral phasor single molecule localization microscopy (SP-SMLM), a hyperspectral and super-resolution method that combines wavefront-like optical filtering with single molecule imaging for simultaneous spatial and spectral analysis. A lab-built three-channel imager with sine/cosine filters encodes emission spectra of single molecules into the phasor space, enabling high-throughput, high-SNR mapping of membrane polarity at sub-50 nm spatial and 15-sec temporal resolutions. Through simulation, we validate that the phasor angle correlates with the spectral mean for single dye molecules. When applied to Nile Red-stained COS-7 cells, SP-SMLM revealed organelle-specific polarity differences and dynamic remodeling of lipid composition within live cells. The methods hyperspectral capability, rapid acquisition, and compatibility with 2D/3D imaging platforms position SP-SMLM as a powerful tool for studying membrane heterogeneity and dynamics in live cells.

biophysics↗

3D multi-omic mapping of whole nondiseased human fallopian tubes at cellular resolution reveals a large incidence of ovarian cancer precursors

Uncovering the spatial and molecular landscape of precancerous lesions is essential for developing meaningful cancer prevention and early detection strategies. High-Grade Serous Carcinoma (HGSC), the most lethal gynecologic malignancy, often originates from Serous Tubal Intraepithelial Carcinomas (STICs) in the fallopian tubes, yet their minute size and our historical reliance on standard 2D histology contribute to their underreporting. Here, we present a spatially resolved, multi-omics framework that integrates whole-organ 3D imaging at cellular resolution with targeted proteomic, metabolomic, and transcriptomic profiling to detect and characterize microscopic tubal lesions. Using this platform, we identified a total of 99 STICs and their presumed precursors that harbor TP53 mutations in morphologically unremarkable tubal epithelium in all five specimens obtained from cancer-free organ donors with average-risk of developing ovarian cancer. Although these lesions comprised only 0.2% of the epithelial compartment, they displayed geographic diversity, immune exclusion, metabolic rewiring, and DNA copy number changes among lesions and normal fallopian tube epithelium discovered alterations in STIC-associated genes and the pathways they control. In sum, this platform provides a comprehensive 3D atlas of early neoplastic transformation, yielding mechanistic insights into tumor initiation and informing clinical screening strategies for detecting cancer precursors in whole organs at cellular resolution.

bioinformatics↗

High Throughput Hyperspectral and Multiplexed Super-Resolution Fluorescence Imaging by SP-STORM

Simultaneous determination of spatial location and spectral color of single molecules at large molecular density with high throughput was achieved by combining single molecule photoswitching and in-hardware transformation based spectral phasor analysis. The method, named spectral phasor enabled stochastic optical reconstruction microscopy (SP-STORM), achieved simultaneous super-resolution imaging of five subcellular structures with minimum crosstalk for the first time. The high throughput feature of SP-STORM enables these subcellular structures to be readily resolved in about one minute, which is more than a magnitude faster than other multiplexing single molecule localization microscopy techniques. The concept of SP-STORM is also compatible with and can be readily applicable to other super-resolution microscopy.

biophysics↗

Differential locus coeruleus-hippocampus interactions during offline states

Patterns of locus coeruleus (LC) activity and norepinephrine (NE) release during non-rapid-eye-movement (NREM) sleep suggest a critical role for the LC-NE system in offline modulation of forebrain circuits. NE transmission promotes synaptic plasticity and is required for memory consolidation, but the field has only begun to uncover how LC activity contributes to coordinated forebrain network dynamics. Hippocampal ripples, a hallmark of memory replay, are temporally coupled with thalamocortical oscillations; however, the circuit mechanisms underlying systems-level consolidation across larger brain networks remain incompletely understood. Here, using multi-site electrophysiology, we examined LC firing in relation to hippocampal ripples in freely behaving rats. LC activity and ripple occurrence were state-dependent and inversely related: heightened arousal was associated with increased LC firing and reduced ripple rates. At finer timescales, LC spiking decreased [~]1-2 seconds before ripple onset, with the strongest modulation during awake ripples but minimal change during ripple-spindle coupling. These findings reveal state-dependent dynamics of LC-hippocampal interactions, positioning the LC as a key component of a cortical-subcortical network supporting systems-level memory consolidation.

neuroscience↗

Massively Parallel Bead-Free Force Spectroscopy with Fluorescence

Single-molecule force spectroscopy (SMFS) has transformed our understanding of biomolecular mechanics. However, current high-throughput implementations rely on beads to apply force, introducing size and surface chemistry variability, requiring per-bead calibration, and are prone to multi-tether artifacts. Long handles further complicate measurements by convolving target conformational changes with handle stretching. We introduce Tether Force Spectroscopy (TFS), a bead-free SMFS platform where a single DNA tether acts as both the force applicator and internal calibrator. In TFS, shear flow acting on identical DNA tethers applies piconewton-scale forces directly to surface-anchored molecules whose conformational dynamics are simultaneously monitored by single-molecule fluorescence. This guarantees single-tether results with uniform, internally calibrated forces and is inherently compatible with single-molecule fluorescence. We achieved high-resolution, high-throughput measurements across hundreds of molecules, enabling both force-extension and rupture experiments without specialized instrumentation. The combination of simplicity and simultaneous force-fluorescence capability makes TFS broadly accessible for correlating structure and function in diverse biomolecular systems.

biophysics↗

BioLab: End-to-End Autonomous Life Sciences Research with Multi-Agents System Integrating Biological Foundation Models

Scientific discovery in the life sciences remains hindered by fragmented workflows, narrow-scope computational models, and inefficient links between in silico prediction and wet-lab validation. We present BioLab, a multi-agent system that integrates domain-specialized foundation models to automate end-to-end biological research. BioLab comprises eight collaborating agents, including a Planner, Reasoner, and Critic, orchestrated through a Memory Agent that enables iterative refinement via retrieval-augmented generation and a suite of 219 computational xBio-Tools spanning five biological scales (DNA, RNA, protein, cell, and chemical). These tools are built on the xTrimo Universe, a collection of 104 models derived from six foundation models (xTrimoChem, Protein, RNA, DNA, Cell, and Text), the majority of which achieve state-of-the-art (91-100% SOTA ratios) on domain benchmarks. Across standard reasoning tasks (PubMedQA, MMLU-Pro/Biology, GPQA-diamond), BioLab consistently outperformed leading large language models, including GPT-4o, Gemini-2.5, and DeepSeek-R1. Beyond benchmarks, BioLab autonomously executed a fully computational pipeline for de novo macrophage-targeting antibody design, progressing from target mining to multi-objective antibody optimization, where molecular dynamics simulations revealed structural mechanisms underlying enhanced affinity of optimized variants. Closing the computational-experimental loop, BioLab designed optimized antibodies (Pem-MOO-1, Pem-MOO-2) that achieved IC50 values of 0.01-0.016 nM, markedly surpassing the parental Pembrolizumab (0.027 nM) for PD-1. Functional assays confirmed enhanced pathway blockade and improved multi-parameter performance profiles. Together, these results establish BioLab as a generalizable framework for AI-native scientific discovery, demonstrating how multi-agent systems coupled with foundation models can autonomously generate, execute, and experimentally validate novel biological hypotheses.

bioinformatics↗

STARNet enables spatially resolved inference of gene regulatory networks from spatial multi-omics data

Biological tissues are composed of distinct microenvironments that spatially orchestrate gene expression and cell identity. However, the regulatory principles governing domain-specific cellular functions remain poorly understood due to the lack of effective methods for mapping gene regulatory networks (GRNs) in situ. To address this gap, we introduce STARNet, a representation learning approach that leverages heterogeneous hypergraph modeling of spatial transcriptomic and epigenomic data to resolve tissue-domain-specific regulatory interactions. By integrating graph neural networks with contrastive learning in a self-supervised framework, STARNet learns unified embeddings that preserve both multi-modal molecular features and anatomical spatial context, enabling accurate and domain-resolved GRN reconstruction within complex tissues. Benchmarking on both simulated and real datasets demonstrates that STARNet achieves state-of-the-art performance. We further demonstrate its broad applicability across diverse biological contexts, including neural development, genetic disease risk, and drug-induced developmental toxicity. In the mouse brain, it delineates region-specific regulatory networks and reconstructs spatiotemporal programs underlying neural stem cell differentiation. In human genetics, it provides a mechanistic link between genotypes and phenotypes by showing how genome-wide association study (GWAS) variants for complex diseases perturb hippocampus-specific GRNs. In developmental toxicology, STARNet reveals that drug-induced disruptions of GRNs in defined embryonic regions underlie tissue-specific vulnerability. Collectively, STARNet offers a powerful and versatile framework for resolving the spatial regulatory logic of complex tissues, providing multi-angle insights into tissue patterning, development, and disease mechanisms.

bioinformatics↗

C9orf72/SMCR8 complex maintains microglial homeostasis via RAB8A-ESCRT-mediated lysosomal repair

Microglia are critical regulators of neuroinflammation and neurodegeneration. Haploinsufficiency of C9orf72, the most common genetic cause of ALS and FTD, has been mainly linked to autophagy-lysosomal pathway defects, but its precise role in microglial lysosomal function remains unclear. Here we identify the C9orf72/SMCR8 complex as a key regulator of microglial homeostasis through lysosomal repair. Loss of C9orf72 and SMCR8 in mice causes age-dependent neuroinflammation and microgliosis, with microglia adopting a disease-associated state. In aged CNS tissue, microglia display lysosomal damage, marked by galectin-3 upregulation and its accumulation on lysosomes. To model this process, we applied the lysosomotropic agent LLOMe to microglia, which recapitulated lysosomal damage and revealed defective recruitment of phosphorylated RAB8A and the ESCRT machinery in C9orf72/SMCR8-deficient cells. Notably, mutant microglia accumulate GTP-bound RAB8A, which becomes aberrantly hyperphosphorylated and mislocalized to non-lysosomal vesicles. We further show that the GAP activity of the C9orf72/SMCR8 complex is essential for lysosomal repair. These findings uncover a previously unrecognized role for the C9orf72/SMCR8 complex in coordinating RAB8A-ESCRT-mediated lysosomal repair, thereby safeguarding microglial homeostasis and limiting neuroinflammation.

cell biology↗

Longitudinal three-photon imaging for tracking amyloid plaques and vascular degeneration in a mouse model of Alzheimer's disease

SignificanceVascular abnormalities may contribute to amyloid-beta accumulation and neurotoxicity in Alzheimers disease (AD). Monitoring vascular degeneration as AD progresses is essential. Three-photon fluorescence microscopy (3PM) enables high-resolution deep tissue imaging with minimal invasiveness and photodamage. AimThis proof-of-concept study established a longitudinal 3P imaging pipeline to quantify vascular and amyloid plaque changes in the APPNL-G-F mouse model. ApproachA cranial window allowed repeated 3P imaging at four-week intervals beginning at five weeks after surgery. Vessels labelled with Texas-Red were segmented using DeepVess, while plaques labelled with methoxy-XO4 were segmented using custom scripts. Quantitative analyses assessed vascular parameters (diameter, tortuosity, length, inter-vessel distance, total volume) and plaque metrics (radius, total volume). ResultsWe imaged the same field over 4 weeks quantifying an overall decrease in vasculature and increase in amyloid plaques between two sessions. Significant changes in vessel diameter, inter-vessel distance, as well as alterations in vessel length and plaques radius were observed. Changes in vessel tortuosity were not significant. ConclusionsWe demonstrate the potential of three-photon imaging to track vascular and amyloid-related changes in deep cortical structures. It offers a tool for studying the interplay between vascular and amyloid pathologies in AD, supporting future research into disease mechanisms and therapeutic strategies.

neuroscience↗

Mediator Subunit MED16 Collaborates with UBP1-TFCP2 to Control Transcriptional Activation or Repression via Promoter Positional Specificity

The Mediator complex acts as a master transcriptional co-regulator, yet the mechanisms by which its individual subunits mediate gene-specific transcription remain incompletely defined. Here, we report that the Mediator subunit MED16 physically associates with the UBP1-TFCP2 heterodimer, which controls the context-dependent transcriptional activation or repression. Biochemical purification combined with mass spectrometry validated MED16 as a bona fide interactor of UBP1-TFCP2. Integrative transcriptomic analyses demonstrated that UBP1 recruits the Mediator complex through MED16 to activate a panel of silenced genes associated with lung homeostasis, angiogenesis and cell proliferation. By contrast, MED16-UBP1 co-occupancy at the HIV-1 transcription start site (TSS) represses viral transcription and sustains HIV latency by compromising pre-initiation complex assembly. Domain-mapping experiments revealed that MED16 must integrate into the intact Mediator complex to exert either activating or repressive function. Genomic analysis uncovered a positional regulatory logic: UBP1-TFCP2 binding motifs adjacent to the TSS promote transcription, while those overlapping the TSS elicit repression. Collectively, our work identifies an MED16-UBP1 regulatory module with dual transcriptional activity and highlights this signaling axis as a potential target for HIV-1 interventions.

biochemistry↗

Generation of effector CD4+ T cells from Human iPSC

Off the shelf CD4+ T cell therapies, particularly those with immunoregulatory or cell repair functions, could be transformative in CAR therapies for cancers and treatment of chronic inflammatory diseases. However, progress is stunted in this area due to challenges generating human CD4+ T cells from induced pluripotent stem cells. Here we describe a key role for the withdrawal of Notch ligand during the final step of stimulation through the T cell receptor to prompt T cell maturation allowing access to the CD4 lineage in iPSC T cells (iCD4+ T cells). Functional analyses of iCD4+ T cells using a novel high-parameter CyTOF intracellular cytokine staining panel revealed both canonical Th1 cytokine signatures and cells producing varying combinations of other cytokines including IL-4, IL-8, and IL-13. Single cell RNA sequencing of iCD4+ T cells demonstrated a transcriptional signature similar to human blood CD4+ T cells. We believe this robust yet simple platform represents a key step towards the generation of off the shelf iCD4+ T cell therapies with utility for the treatment of a panoply of diseases including cancer and inflammatory autoimmune disorders. HIGHLIGHTST cell receptor stimulation of iPSC CD4+/CD8+ T cell progenitors on coating without Notch ligand allows access to the CD4+ T cell lineage iPSC derived CD4+ T cells express varied cytokines in response to stimulation

immunology↗

The 3D genome of pediatric B-cell precursor acute lymphoblastic leukemia

Whereas the molecular pathogenesis of childhood B-cell precursor acute lymphoblastic leukemia (BCP ALL) has been studied extensively, its 3D chromatin landscape - of vast importance for gene regulation - remains poorly explored. Here, we applied Micro-C, a high-resolution variant of Hi-C, to 35 primary pediatric BCP ALL cases, spanning all major genetic subtypes. We present a complete view of the chromatin interaction landscape in childhood ALL, with resolutions reaching up to 5 kb in individual samples and 1 kb in the aggregated dataset. Somatic genetic aberrations - including fusion genes, aneuploidy, and structural variants - were found to profoundly reshape the 3D genome organization, impacting chromatin compartmentalization (A/B), topologically associating domain (TAD) architecture, and regulatory element positioning. Notably, chromosomal gains were associated with weakened TAD boundaries and widespread gene dysregulation. In addition, our analysis identified over 25,000 chromatin loops anchored at regulatory elements--e.g., enhancer-promoter loops--regulating the expression of more than 10,000 protein-coding genes. Among these, we highlight regulatory loops that drive gene expression differences between BCP ALL subtypes in the absence of concurrent somatic genetic aberrations, including the known driver genes HOXA9, FLT3, TP53, CD44, IKZF1, ERG, and XBP1. Taken together, our study gives unprecedented insights into chromatin organization and gene regulation in the leukemogenesis of BCP ALL.

cancer biology↗

ProteinReasoner: A Multi-Modal Protein Language Model with Chain-of-Thought Reasoning for Efficient Protein Design

Reasoning has emerged as a central capability of large language models, yet how it should be formulated for scientific foundation models remains unclear because scientific knowledge is distributed across interdependent, domain-specific representations. Here we introduce modality-chain reasoning, which organizes representations into ordered computational chains, each conditioning prediction or generation of the next. Based on this principle, we develop ProteinReasoner, a multimodal generative protein foundation model that sequentially connects amino acid sequence, evolutionary constraints and three-dimensional structure within a shared autoregressive architecture. Across zero-shot structure prediction, inverse folding and fitness prediction, ProteinReasoner outperformed two multimodal protein foundation models, while controlled comparisons supported the functional contribution of the modality chain. We further extended this principle beyond pretraining: reorganizing the chain across successive structural states enabled multiple-conformation prediction, while introducing experimental feedback as an additional modality enabled an in-context learning paradigm for protein optimization without target-specific parameter updates. In particular, across thermostability and affinity-maturation evaluations, this paradigm improved over matched fine-tuned models and showed stronger mean performance than target-specific active-learning baselines. These results establish modality-chain reasoning as a unified and effective foundation-modelling strategy in protein science. More broadly, they suggest a general route towards reasoning across interdependent representations in other scientific domains.

bioinformatics↗

The Fengshu Large Model for Wugu Fengdeng: An Innovation Engine for Knowledge Integration in the Soybean Field

Against the backdrop of global population growth and the continuous escalation of food demand, the acceleration of agricultural modernization has emerged as the core pathway to safeguard food security. As the worlds fourth-largest food crop, soybean (Glycine max) possesses multiple strategic values for food security, livestock feed, and industrial raw materials, thanks to its high protein content (accounting for over 40% of the dry weight of seeds) and oil resource attributes. However, the soybean industry is confronted with multiple challenges: the long cycle of genetic breeding (8-10 years required by traditional methods), annual losses from diseases and pests reaching 40% (data from FAO 2023), and the reliance on empirical decision-making in field management, all of which urgently call for intelligent solutions.At present, agricultural knowledge is experiencing explosive growth - more than 4,000 new soybean-related literatures are added annually in PubMed, and agricultural technology Q&A platforms (Zhihu, Baidu Tieba, etc.) generate over 3,000 daily questions. However, this multi-source heterogeneous knowledge is scattered in books, literatures, Q&A communities, and gene databases, lacking systematic integration, resulting in a knowledge utilization rate of less than 30%. In response to this, this paper proposes the "Fengshu-Agri" large model, an agricultural knowledge integration and innovation engine based on the collaboration of Retrieval-Augmented Generation (RAG) and Knowledge Graph (KG). The model achieves breakthroughs through the following core technological innovations: O_LIDeep integration of multi-source heterogeneous data: For the first time, a systematic integration of 256 agricultural monographs (covering standardized knowledge such as planting techniques and pest control), 66,772 cutting-edge research literatures (genomics, agronomic trait analysis, etc.), 880,000 production practice Q&A (covering scenarios such as pest diagnosis and environmental stress response), and 120,000 gene annotation data (functional genes, expression regulation mechanisms) has been carried out to construct the largest knowledge graph in the agricultural field - containing 2 million entity nodes, realizing full-chain knowledge modeling from molecular-level gene regulation to field management. C_LIO_LIDouble-layer collaborative retrieval mechanism: Innovatively integrating RAG semantic vector retrieval with KG structured reasoning to solve problems such as low recall rate (<65%) and semantic ambiguity in traditional systems. Specifically, it achieves dual matching through local keywords (entity-level) and global keywords (relationship-level); C_LIO_LIOptimization of domain-specific generation engine: Based on the QWEN-QWQ32B large language model, a three-stage fine-tuning is carried out (pre-training, agricultural instruction fine-tuning, and reinforcement learning from human feedback) [15], which improves the professionalism of generated texts by 35% (manual evaluation index) and significantly reduces the LLM hallucination problem [12]. Experimental results show that Fengshu-Agri achieves an accuracy rate of 89.6% in soybean knowledge retrieval tasks (a 25.4% improvement over traditional RAG models), a recall rate of 87.3% (20.5% higher than pure KG reasoning models), and an F1 score of 88.4%. It can efficiently answer complex questions involving multi-entity associations (such as "the impact mechanism of CRISPR-editing the GmSWEET gene on lepidopteran pest resistance"). Analysis of typical cases indicates that the models responses not only cover technical principles (sgRNA design, Agrobacterium transformation procedures) but also integrate metabolomics data (70% improvement in insect resistance with no significant yield reduction), demonstrating cross-modal knowledge fusion capabilities. In the future, this model will be expanded to crops such as maize and potato to construct an agricultural intelligent ecosystem covering the entire process of cultivation management and breeding improvement, promoting the upgrading of precision agriculture toward a data-driven model. C_LI

plant biology↗

Dissecting Tissue Architecture and Function through Mapping of Cellular Communication Networks

Spatial transcriptome provides critical insights for inferring cell-cell communications. Based on the heuristic that physically adjacent cells are more likely to communicate with each other, we develop a computational framework that Infers the Cell-Cell Communication network (IC3) and subsequently identifies communication hotspots with rigorous error control. We demonstrate in simulations and real datasets that our method outperforms existing methods in accuracy and especially improves sensitivity to identify communications involving rare cell types. Applying IC3 in a mouse brain dataset, we recovered how cells communicate with each other to form a local structure that regulates the balance of the blood-brain barrier. These findings highlight that our method is effective in revealing tissue architecture and function from cellular communication networks.

bioinformatics↗

Algal Optics

Nearly a decade ago it was discovered that the spherical cell body of the alga Chlamydomonas reinhardtii can act as a lens to concentrate incoming light onto the cells membrane-bound photoreceptor and thereby affect phototaxis. Since many nearly transparent cells in marine environments have complex, often non-axisymmetric shapes, this observation raises fundamental, yet little-explored questions in biological optics about light refraction by the bodies of microorganisms. There are two distinct contexts for such questions: the absorption problem for incoming light, typified by photosynthetic activity taking place in the chloroplasts of green algae, and the emission problem for outgoing light, where the paradigm is bioluminescence emitted from scintillons within dinoflagellates. Here we examine both of these aspects of "algal optics" in the special case where the absorption or emission is localized in structures that are small relative to the overall organism size, taking into account both refraction and reflections at the cell-water boundary. Analytical and numerical results are developed for the distribution of light intensities inside and outside the body, and we establish certain duality relationships that connect the incoming and outgoing problems. For strongly non-spherical shapes we find lensing effects that may have implications for photosynthetic activity and for the angular distribution of light emitted during bioluminescent flashes.

biophysics↗

Single oocyte full-length isoform sequencing unveils the impact of transposable elements on RNA diversity and stability during oocyte maturation

The oocyte-specific isoforms play crucial roles in oocyte maturation, while current understanding of the oocyte transcriptome is mainly focused on gene level. Here, we utilized single cell full-length isoform sequencing based on third generation sequencing to detect entire transcripts in human and mouse oocytes. Isoform diversity during oocyte maturation was systematically profiled, including 6,736 and 4,902 putative novel human and mouse transcripts, respectively. More than half of novel isoforms were categorized as the novel-not-in-catalog (NNC) and may serve specific functions in oocytes, including novel isoforms of ARHGAP18, colocalized with microtubules and targeted knockdown disrupting oocyte maturation. Moreover, over 25% of NNC isoforms were derived from transposable elements (TEs), and their incorporation within transcripts could enhance isoform stability during oocyte maturation. Altogether, our findings represent a valuable resource showcasing the complexity and diversity of RNA isoforms in oocytes, as well as TE co-option for novel isoform generation and isoform stability enhancement.

developmental biology↗