Biology subjects

Qiu, W.

Publications and source records attributed to Qiu, W..

At least 19 recordsLinked to original sources

bioRxiv2026

Non-cell-autonomous removal of protein aggregates via trogocytosis

Protein aggregate formation can cause cell damage and contribute to tissue pathologies including neurodegeneration. Protein aggregates are normally eliminated by cell-intrinsic mechanisms of lysosomal (autophagic) degradation. However, degradative capacity varies between cell types, raising the possibility that high-capacity cell types, such as macrophages, may contribute to aggregate disposal from the low-capacity cells. Here, we show that cellular protein aggregates are removed by macrophages via trogocytosis -- a partial engulfment of the target cells. Lysosomal stress upon protein aggregate accumulation promotes cell surface expression of the transmembrane isoform of the macrophage growth factor CSF1 (tmCSF1), which is detected by macrophages through the CSF1 receptor to drive trogocytosis. Insufficient or impaired degradation of protein aggregates in lysosomes results in their transport along microtubules to the plasma membrane where they physically associate with tmCSF1. This enables macrophages to specifically trogocytose protein aggregates. These findings reveal a protein homeostasis system that eliminates protein aggregates in a non-cell-autonomous manner.

cell biology↗

bioRxiv2026

Organelle Volume Facilitates Spindle Positioning During C. elegans Female Meiosis

Cortical positioning of oocyte meiotic spindles is required for reducing chromosome number by segregating chromosomes into polar bodies. In C. elegans, kinesin-1 transports membrane-bound organelles inward into a central ball that is hypothesized to push the meiotic spindle outward. Using focused ion beam scanning electron microscopy, we found that the percent volume occupied by membrane-bound organelles was 28% in a mature oocyte that has completed endocytosis of the yolk precursor, vitellogenin, compared to 17% in a less mature oocyte that has not yet endocytosed vitellogenin. We therefore hypothesized that blocking endocytosis of vitellogenin would reduce the size of the central ball of organelles packed inward by kinesin-1 and limit outward movement of the spindle. Depletion of vitellogenin or proteins required for endocytosis resulted in a smaller central volume of kinesin-coated organelles and defective spindle positioning. A computer simulation of a simple exclusion model faithfully recapitulated wildtype and mutant spindle position phenotypes. These results support a volume exclusion model for positioning acentriolar meiotic spindles.

cell biology↗

bioRxiv2026

IL-21-producing peripheral helper T cells associate with autoimmune bile duct injury in biliary atresia

BackgroundBiliary atresia (BA) is a severe neonatal liver disease characterized by progressive fibrosis and bile duct obliteration. ObjectiveAlthough immune dysregulation is implicated in the pathogenesis of BA, the specific mechanisms driving bile duct injury remain incompletely understood. This study aimed to characterize tertiary lymphoid structures (TLSs) within extrahepatic biliary remnants (EBRs), identify their cellular mediators, and evaluate the therapeutic potential of targeting IL-21 receptor signaling. DesignWe performed integrated bulk RNA sequencing, single-cell RNA sequencing, spatial transcriptomics, multiplex immunohistochemistry, and flow cytometry on clinical samples from BA patients and non-BA cholestatic controls. TLS maturation was assessed by CD23 immunohistochemistry in EBRs from 148 BA patients and correlated with clinical parameters. Anti-IL-21R antibody treatment was evaluated in a rhesus rotavirus-induced BA mouse model, with treatment initiated on day 4 post-infection. ResultsTLSs were identified in BA EBRs with significantly higher prevalence than in matched liver tissues. Mature TLSs containing CD23 germinal centers were associated with elevated serum matrix metalloproteinase-7, more advanced hepatic fibrosis, and localized autoantibody deposition on injured bile ducts. Single-cell profiling revealed expanded CD4+ T peripheral helper (Tph) cells expressing IL-21 and CXCL13 within TLS-containing EBRs. Tph cells were enriched in peripheral blood of BA patients compared to non-BA cholestatic controls (P = 0.0025), and serum IL-21 was significantly elevated (P < 0.0001). Post-infection IL-21R blockade in the mouse model reduced jaundice incidence, improved weight gain, prevented extrahepatic biliary obstruction, and significantly improved long-term survival. ConclusionTLSs in BA extrahepatic biliary remnants harbor expanded Tph cells associated with IL-21-mediated B cell activation and bile duct injury. IL-21R blockade ameliorated disease in a murine BA model, identifying the IL-21/IL-21R axis as a potential therapeutic target warranting further investigation. Key MessagesO_ST_ABSWhat is already known on this topicC_ST_ABSImmune dysregulation contributes to biliary atresia (BA), with documented lymphocyte infiltration and defective B cell tolerance. However, the cellular mechanisms linking local immune activation to bile duct injury are unclear, and the roles of organized lymphoid structures and specific CD4 T cell subsets in orchestrating local humoral responses have not been characterized. What this study addsThis study demonstrates that mature tertiary lymphoid structures in extrahepatic biliary remnants are associated with disease severity markers and localized bile duct injury in BA. We identify T peripheral helper cells as an expanded IL-21-producing CD4 T cell population within these structures, and show that post-infection IL-21 receptor blockade prevents biliary obstruction and improves survival in a murine BA model. How this study might affect research, practice or policyThese findings identify the IL-21/IL-21R signaling axis as a candidate therapeutic target in BA warranting further preclinical and translational investigation. TLS maturation status in biliary remnants and serum autoantibody levels may serve as potential biomarkers of disease severity, meriting prospective evaluation in clinical cohorts.

immunology↗

bioRxiv2026

SUMO mediates the coordinate regulation of meiotic chromosome length and crossover rate

Meiotic prophase-I chromosomes are organized into linear arrays of chromatin loops anchored to proteinaceous axes that define the interaction interfaces for the pairing and synapsis of homologous chromosomes. Chromatin loop size and axial chromosome length are inversely correlated and vary widely both between and within species, including between the sexes. The molecular basis of this variation remains unclear. Here, we provide evidence that the small ubiquitin-like modifier, SUMO, regulates loop-axis organization in mouse meiosis. Our analysis shows that the longer axes of oocyte chromosomes contain more SUMO per unit length than the shorter axes of spermatocyte chromosomes. In mouse models, the loss of SUMO1 results in shorter axes and longer chromatin loops. Conversely, increased SUMO1 conjugation, caused by mutation of the SENP1 isopeptidase, produces longer axes with shorter loops. Axis length positively correlates with meiotic recombination. Accordingly, Sumo1 and Senp1 mutations respectively decrease and increase crossover frequency. These findings identify SUMO as a key regulator of meiotic chromosome architecture and suggest a molecular basis for the physiological variation in chromosome length and recombination rates seen among species, sexes, individuals, and individual meiocytes. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/710713v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@145c465org.highwire.dtl.DTLVardef@160c8aborg.highwire.dtl.DTLVardef@1165b76org.highwire.dtl.DTLVardef@ced5e0_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2026

Bacterial exo-α-sialidases subvert the complement system through desialylation

The complement system is a central pillar of innate immunity, yet how bacterial glycan-modifying enzymes subvert complement function remains poorly understood. Bacterial sialidases remove terminal sialic acids from host sialoglycans, but their direct impact on complement immunity is unclear. Here, we investigate the impact of six sialidases from five human pathogens on complement immunity using an integrated approach combining genetics, biochemistry, glycobiology, mass spectrometry, and structural biology. We demonstrate that major complement components (IgG, C1q, C4, and C5) and regulators (Factor I, Factor H, and C4bp) are sialylated, and that bacterial sialidase-mediated desialylation suppresses complement activation and surface deposition, thereby enabling complement evasion. Despite extensive sequence diversity, biochemical and structural analyses reveal that all examined sialidases share a conserved six-bladed {beta}-propeller catalytic domain and cleave both N-acetylneuraminic and N-glycolylneuraminic acids, the predominant mammalian sialic acids. Together, these findings uncover a conserved mechanism by which diverse bacterial pathogens disable complement immunity through desialylation.

microbiology↗

bioRxiv2026

DeepUnitMatch: tracking neurons across days in electrophysiology using Deep Neural Networks

To understand neural processes such as learning or memory, we need to track the activity of populations of neurons at the level of single spikes and across days. Here, we leverage deep neural networks to build DeepUnitMatch, a software that reliably tracks individual neurons in high-density electrophysiological recordings across weeks. DeepUnitMatch uses only the spike waveforms of the neurons, and not their spiking patterns, and outperforms current solutions.

neuroscience↗

bioRxiv2025

Metabolic dysfunction related to specific genetic variant sites of methylmalonic acidemia

Methylmalonic acidemia (MMA) is a genetic metabolic disease, with mut (mut-MMA, caused by MMUT gene variation) and cblC (cblC-MMA, caused by MMACHC gene variation) being the predominant subtypes. MMA patients carrying c.729_730insTT and c.609G>A exhibit severe clinical manifestations and have poorer outcomes. Little information is known on the potential mechanism. The metabotypes of MMA patients carrying c.729_730insTT and c.609G>A were profiled. The potential effect of genetic variation sites on the metabolism were explored. Leveraging the gene variation spectrum and the targeted metabolomics, propionic acid, indolelactic acid, myristoleic acid, tetradecenoic acid, tridecanoic acid, and oxoadipic acid showed strong enrichment in c.729_730insTT carrying mut-MMA patients. Whereas mutation c.609G>A caused adipic acid, pimelic acid, fructose, AMP, hexanylcarnitine, and methionine significnatly altered in cblC-MMA patients. Furthermore, the metabolomic profiles were obviously different in c.729_730insTT and non-c.729_730insTT carrying mut-MMA patients after treatment. Different metabolic alterations in cblC-MMA patients carrying c.609G > A and non-c.609G > A under treatment were also observed. Our findings provide unique insights into the metabolic basis of MMA specific subtypes and its implications across different variants.

molecular biology↗

bioRxiv2025

To explore the role of NABP2 in the immune microenvironment and metabolic pathway of liver cancer

ObjectiveThis study aims to explore the specific signaling pathways associated with the NABP2 gene and its potential molecular mechanisms influencing the progression of hepatocellular carcinoma (HCC), thereby identifying new therapeutic targets. MethodWe collected 50 normal and 374 tumor samples to investigate the differential expression of NABP2 in HCC. Variousgenomic, single-cell, and bioinformatic analyses, including gene microarray technology, were employed. Data processing and analysis were conducted using R language, focusing on the correlation between NABP2 expression, immune cell infiltration, drug sensitivity, and metabolic pathways. ResultsOur findings indicate that NABP2 plays a significant role in the development of HCC and the tumor immune microenvironment. Analyses such as GSVA and GSEA suggest that NABP2 may influence disease progression through involvement in key molecular signaling pathways, including DNA replication, mRNA splicing, and protein degradation. Furthermore, a notable correlation was observed between NABP2 and various metabolic pathways, as well as specific immune cell populations. Additionally, we identified potential chemotherapeutic agents for HCC based on drug sensitivity analysis. ConclusionThese findings position NABP2 as a crucial biomarker for the progression and treatment of hepatocellular carcinoma, offering new insights into the pathogenesis and prognostic strategies for HCC in future research.

bioinformatics↗

bioRxiv2025

A Syngeneic Immunocompetent Mouse Model of Gallbladder Cancer Reveals Tumorigenesis and Therapeutic Response

PurposeGallbladder cancer (GBC) is a rare but highly lethal malignancy with one of the poorest prognoses among cancers of the digestive system cancers. However, current experimental models of GBC face critical limitations, particularly their dependence on immunodeficient hosts, which precludes the investigation of the tumor microenvironment. We aimed to establish a novel syngeneic immunocompetent mouse model that recapitulates human GBC and enables the investigation of tumor-immune interactions. Experimental DesignWe engineered a murine cell line (mGBC1-ZH) from normal mouse gallbladder organoids expressing Kras and Trp53 (encoding mouse p53) mutations. Tumorigenic potential of mGBC1-ZH was evaluated by subcutaneous and orthotopic implantation. RNA-Seq and WES was used to demonstrate its characterization and similarity with human GBC. Immunohistochemistry, CCK8, and transwell assays wereused to investigate the role of CXCL5 in GBC. Therapeutic responses to standard first-line chemotherapeutic agents was evaluated in the syngeneic GBC model. ResultsThis model supports both subcutaneous and orthotopic tumor growth in immunocompetent C57BL/6J hosts while preserving hallmark features of human GBC, including biliary epithelial differentiation (CK7+/CK19+), aggressive histopathology, and an immunosuppressive "cold" tumor microenvironment. Genomic characterization revealed recurrent chromosomal instability and copy number alterations mirroring human GBC. Comprehensive transcriptomic profiling revealed profound gene expression changes during the model development, and resembled transcriptional features between mGBC1-ZH and human GBC cell lines and samples. CXCL5 was found to be upregulated in human GBC, and promote proliferation, metastasis, and neutrophils infiltration of GBC in the syngeneic mouse model. Functional validation of the syngeneic GBC model demonstrated therapeutic responsiveness to frontline chemotherapeutics gemcitabine and cisplatin with significant in vivo tumor regression. ConclusionsIn summary, we establised a novel syngeneic GBC mouse model, overcoming the limitations of traditional models by enabling studies in immunocompetent hosts. This model provides valuable insights into the molecular evolution from normal gallbladder cells to transformed cancer cells and establishes a robust platform for both mechanistic studies and therapeutic development.

cancer biology↗

bioRxiv2025

An Explainable AI Framework for Identifying Universal Aging Signatures in Cell Embeddings

Aging is a complex biological process marked by progressive physiological decline and increased disease vulnerability. Single-cell RNA sequencing offers unprecedented resolution for studying aging, yet isolating aging-related signatures remains challenging because gene expression is primarily shaped by other factors such as cell type, tissue, and sex. We present ACE (Aging Cell Embeddings), an explainable deep generative framework that disentangles aging-related gene expression changes from background biological variation. ACE employs two latent representations: one capturing aging-related signatures and another representing non-aging-related variation in the data. Through explainable AI, ACE identifies key genes and pathways associated with aging amid dominant non-aging-related variations. Applied to large-scale mouse, fly, and human datasets, ACE uncovers aging signatures both within specific tissue-cell-type contexts and across all tissues and cell types, enabling accurate prediction of biological age. Moreover, ACE identifies aging genes conserved across species, highlighting its ability to reveal shared biological mechanisms of aging. Experimental RNAi knockdowns in C. elegans validate ACEs findings, confirming its ability to prioritize novel aging genes affecting lifespan. ACE reveals key pathways involved in proteostasis, immune regulation, and extracellular matrix remodeling, and identifies Uba52 through the cross-species model as an important aging gene, whose knockdown in C. elegans significantly shortens lifespan. By providing interpretable and generalizable aging embeddings, ACE establishes a foundation for cross-species single-cell aging studies and translational geroscience.

bioinformatics↗

bioRxiv2025

Sexual dimorphism in the complete connectome of the Drosophila male central nervous system

Sex differences in behaviour exist across all animals, typically under strong genetic regulation. In Drosophila, fruitless/doublesex transcription factors can identify dimorphic neurons but their organisation into functional circuits remains unclear. We present the connectome of the entire Drosophila male central nervous system. This contains 166,691 neurons spanning the brain and nerve cord, fully proofread and annotated including fruitless/doublesex expression and 11,691 types. We provide the first comprehensive comparison between male and female brain connectomes to synaptic resolution, finding 7,205 isomorphic, 114 dimorphic, 262 male-specific and 69 female-specific types. This resource enables analysis of full sensory-to-motor circuits underlying complex behaviours and the impact of dimorphic elements. Sex-specific/dimorphic neurons are concentrated in higher brain centres while the sensory and motor periphery are largely isomorphic. Within higher centres, male-specific connections are organised into hotspots defined by male-specific neurons or arbours. Numerous circuit switches reroute sensory information to form antagonistic circuits controlling opposing behaviours.

neuroscience↗

bioRxiv2025

Alternating Angle Milling Suppresses Streaking Artifacts in FIB-SEM Imaging

Focused ion beam scanning electron microscopy (FIB-SEM) (1-3) has been used in life sciences to produce large volumetric datasets with high resolution information on ultrastructure of biological organisms. 3D image acquisition is accomplished by serial removal of thin layers of material using focused ion beam (FIB) milling followed by scanning electron microscopy (SEM) imaging. One of the challenges in the standard FIB-SEM imaging protocol is that FIB milling results in characteristic artifacts, known as "streaks" or "curtains". These streaks are caused by non-uniform material removal forming long straight trenches parallel to the FIB milling direction. These artifacts get worse along the milling direction and ultimately limit size of the SEM field of view. Various methods have been proposed to mitigate the streaks in acquired images. While these techniques often provide noticeable visual improvement, the underlying problem remains. The structural information in the "streaked" areas is lost due to non-uniform material removal during milling and cannot be fully recovered. We propose a simple modification allowing for a significant reduction of milling non-uniformities of streaks. We demonstrate the effectiveness of this approach on various samples.

cell biology↗

bioRxiv2025

Germline Targeted Baboon Apolipoprotein L-1 Protects Mice Against African Trypanosomes

Certain primates are immune to infection by most African trypanosome parasites due to apolipoprotein L-1 (APOL1), a primate-specific ion channel-forming protein. To broaden our understanding of primate APOL1, we generated a panel of trypanosome-resistant murine models expressing various primate APOL1 proteins. We used these mice to investigate the role of APOL1 in trypanosome immunity in vivo by challenging them with various human and livestock trypanosome isolates. Baboon APOL1 provides partial protection to trypanosome isolates, though its protective capacity was limited by poor expression. A more highly expressed chimeric APOL1 encoding human APOL1 with the baboon APOL1 C-terminus was protective against human-infective trypanosomes, although with a fitness cost likely associated with high expression. We investigated the long-standing assumption that human resistance to Trypanosoma vivax is mediated by APOL1. Surprisingly, APOL1-expressing mice were fully susceptible to T. vivax infection, challenging this hypothesis. These model systems are useful tools for evaluating the possibility of generating genetic engineered livestock for disease control.

microbiology↗

bioRxiv2025

Localized Space Coding and Phase Coding Complement Each Other to Achieve Robust and Efficient Spatial Representation

Localized space coding and phase coding are two distinct strategies responsible, respectively, for representing abstract structure and sensory observations in neural cognitive maps. In spatial representation, localized space coding is implemented by place cells in the hippocampus (HPC), while phase coding is implemented by grid cells in the medial entorhinal cortex (MEC). Both strategies have their own advantages and disadvantages, and neither of them meets the requirement of representing space robustly and efficiently in the brain. Here, we show that through reciprocal connections between HPC and MEC, place and grid cells can complement each other to overcome their respective shortcomings. Specifically, we build a coupled network model, in which a continuous attractor neural network (CANN) with position coordinate models place cells, while multiple CANNs with phase coordinates model grid cell modules with varying spacings. The reciprocal connections between place and grid cells encode the correlation prior between the sensory cues processed by HPC and MEC, respectively. Using this model, we show that: 1) place and grid cells interact to integrate sensory cues in a Bayesian manner; 2) place cells complement grid cells in coding accuracy by eliminating non-local errors of the latter; 3) grid cells complement place cells in coding efficiency by enlarging the number of environmental maps stored stably by the latter. We demonstrate that the coupled network model explains the seemingly contradictory experimental findings about the remapping phenomena of place cells when grid cells are either inactivated or depolarized. This study gives us insight into understanding how the brain employs collaborative localized and phase coding to realize both robust and efficient information representation.

neuroscience↗

bioRxiv2025

Unravelling the anti-cancer mechanisms elicited by non-covalent thioredoxin reductase inhibitors for triple negative breast cancer therapy.

Thioredoxin reductases (cytosolic TXNRD1 and mitochondrial TXNRD2) are antioxidant enzymes often overexpressed in tumors, including triple negative breast cancer (TNBC), making them promising targets for cancer therapy. Inhibiting these enzymes may worsen the already elevated oxidative stress in cancer cells, ultimately leading to cell death through a pro-oxidant mechanism. However, selectively targeting TXNRDs has been challenging due to the traditional reliance on covalent inhibition strategies. Recent studies have identified a druggable allosteric pocket in this enzyme family, paving the way for the development of novel non-covalent inhibitors, referred to as TXNRD(i)s. These inhibitors have been tested in TNBC models and have demonstrated a range of anti-cancer effects. To understand the molecular and cellular consequences of TXNRD(i)s, we conducted unbiased transcriptomic analyses and found that the gene expression changes induced by TXNRD(i) treatment closely mirror those resulting from TXNRD1 silencing, reinforcing TXNRD1 as the primary therapeutic target. While TXNRD(i) treatment increases redox stress in TNBC cells, this is not the main driver of the anti-cancer effect. Instead, TXNRD(i)s potently inhibit cell proliferation and induce G1 phase cell cycle arrest. Notably, supplementing cells with exogenous deoxynucleotides restores cell viability, cell cycle progression and partially reverses cell death. These findings indicate that TXNRD(i)s deplete endogenous deoxynucleotide pools and impair ribonucleotide reductase activity as the main mechanism of anti-cancer effects. We further demonstrate that TXNRD(i)s inhibit both TXNRD1 and TXNRD2, and that dual inhibition is more effective in suppressing TNBC cell growth. In vivo, TXNRD(i) treatment significantly impairs TNBC xenograft tumor growth and reduces proliferation-related genes. Collectively, these findings challenge the prevailing paradigm that all TXNRD inhibitors function through a pro-oxidant mechanism, instead highlighting that non-covalent TXNRD(i)s exert their effects by blocking proliferation offering a compelling therapeutic strategy for TNBC and potentially other cancers with elevated TXNRD expression. HighlightsNon-covalent TXNRD inhibitors increase intracellular redox stress, but this is not the main driver of anti-cancer effects TXNRD(i)s inhibit both cytosolic TXNRD1 and mitochondrial TXNRD2 enzymes Both TXNRD1 and TXNRD2 are required for growth and proliferation of triple negative breast cancer cells Halted proliferation through ribonucleotide reductase dysfunction emerges as the primary driver of anti-cancer effect Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=174 HEIGHT=200 SRC="FIGDIR/small/674327v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1b5638aorg.highwire.dtl.DTLVardef@19a117eorg.highwire.dtl.DTLVardef@1f27e95org.highwire.dtl.DTLVardef@1549862_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2025

Engineering lung-sensing T cells using synthetic receptors targeting RAGE

Our goal was to leverage synthetic biology approaches to engineer lung-sensing T cells that trigger synthetic transcriptional programs only when in the lung. First, we identified a lung-specific cell surface protein, receptor for advanced glycation endproducts (RAGE), expressed at high levels exclusively in the lung. Then, we engineered chimeric antigen receptors (CAR) and synthetic notch receptors (SynNotch) to bind this protein. We showed that anti-RAGE CAR-T cells traffic to and proliferate in the lung exclusively. Anti-RAGE SynNotch receptors activate transcription of a fluorescent reporter only when co-cultured with RAGE+ cell lines or primary lung cells. Finally, we tested an anti-RAGE SynNotch to anti-CD19 CAR circuit in vivo in mice implanted with lung and flank tumors and found that this approach cleared CD19-expressing lung tumors without affecting CD19-expressing flank tumors. Thus, we demonstrate that RAGE is a lung-specific target and that T cells expressing anti-RAGE receptors can sense and activate lung-specific therapeutic transcriptional programs. This approach could be extended to allow cell-based therapies that target and deliver genetically encoded payloads to treat lung diseases while avoiding systemic toxicity.

synthetic biology↗

bioRxiv2025

Clonal Expansion of Alveolar Fibroblast Progeny Drives Pulmonary Fibrosis

Pulmonary fibrosis has been called a fibroproliferative disease but the functional importance of proliferating fibroblasts to pulmonary fibrosis has not been systematically examined. In response to alveolar injury, resting alveolar fibroblasts differentiate into fibrotic fibroblasts that express high levels of collagens. However, what role, if any, proliferation plays in the accumulation of fibrotic fibroblasts remains unclear. Through EdU incorporation, genetic lineage tracing, and single cell RNA sequencing, we resolve the proliferation dynamics of lung fibroblasts during post-injury fibrogenesis. Our data show substantial DNA replication in progeny of alveolar fibroblasts in two models of pulmonary fibrosis. By genetically labeling individual cells, we observe clonal expansion of alveolar fibroblast descendants principally in regions of fibrotic remodeling. The transcriptome of proliferating fibroblasts closely resembles that of fibrotic fibroblasts, suggesting that fibroblasts can first differentiate into fibrotic fibroblasts and then proliferate. Genetic ablation of proliferating fibroblasts and selective inhibition of cytokinesis in alveolar fibroblast descendants significantly mitigates pulmonary fibrosis and rescues lung function. Furthermore, fibroblasts in precision-cut lung slices from human fibrotic lungs exhibit higher proliferation rates than those in non-diseased lungs. This work establishes fibroblast proliferation as a critical driver of pulmonary fibrosis and suggests that specifically targeting fibroblast proliferation could be a new therapeutic strategy for fibrotic diseases.

cell biology↗

bioRxiv2025

The China Brain Multi-omics Atlas Project (CBMAP)

The China Brain Multi-omics Atlas Project (CBMAP) aims to generate a comprehensive molecular reference map of over 1,000 human brains (Phase I), spanning a broad age range and multiple regions in China, to address the underrepresentation of East Asian populations in brain research. By integrating genome, epigenome, transcriptome, proteome (including multiple post-translational modifications), and metabolome data, CBMAP is set to provide a rich and invaluable resource for investigating the molecular underpinnings of aging-related brain phenotypes and neuropsychiatric disorders. Leveraging high-throughput omics data and advanced technologies, such as spatial transcriptomics, proteomics, and single-nucleus 3D chromatin structure analysis, this atlas will serve as a crucial resource for the brain science community, illuminating disease mechanisms and enhancing the utility of data from genome-wide association studies (GWAS). CBMAP is also poised to accelerate drug discovery and precision medicine for brain disorders.

neuroscience↗