Biology subjects

Zhang, C.

Publications and source records attributed to Zhang, C..

At least 307 records · Page 17Linked to original sources

bioRxiv2025

Microbes under climatic refugia: Self-stabilizing subcommunity rank dynamics in large-river deltaic estuaries

Microorganisms, akin to macroorganisms, can be sheltered by climatic refugia, overlooked for optimism about microbial extinction. By categorizing microbial communities into ecologically distinct subcommunities, we conducted a two-year survey of large-river deltaic estuaries (LDEs) which are regarded as refugial hotspots, and established rank hierarchies to monitor temporal changes. We found that, consistent with macroecology, LDEs harbor distinct microbial community structures, with the abundance distribution of subcommunities exhibiting resilience against environmental perturbations, persisting on an annual cycle. In particular, while the evenness of subcommunity rank abundance curves fluctuates frequently, shifts in rank order are less dynamic but, once initiated, have a more pronounced impact on subsequent rank dynamics. Our results suggest that the microbial subcommunity rank structure in LDEs is both persistent and robust, aligning with classic patterns of species abundance distributions. This study emphasizes that, despite differences in their roles, the stable functioning of microbial rank systems is also fundamental to the refugial capacity of ecosystems and should be given equal importance.

ecology↗

bioRxiv2025

TransBrain: A computational framework for translating brain-wide phenotypes between humans and mice

Despite remarkable advances in whole-brain imaging technologies, the lack of quantitative approaches to bridge rodent preclinical and human studies remains a critical challenge. Here we present TransBrain, a computational framework enabling bidirectional translation of brain-wide phenotypes between humans and mice. TransBrain improves human-mouse homology mapping accuracy through: (1) a novel detached region-specific deep neural network trained on integrated multi-modal human transcriptomics to improve cortical correspondence (89.5% improvement over the original transcriptome), which revealed two evolutionarily conserved gradients explaining >50% of cortical organizational variance, and (2) random walk-based graph representation learning to construct a unified cross-species latent space incorporating anatomical hierarchies and structural connectivity. We demonstrated TransBrains utility through three cross-species applications: quantitative assessment of resting-state brain organizational features, inferring human cognitive functions from mouse optogenetic circuits, and translating molecular insights from mouse models to individual-level mechanisms in autism. TransBrain enables quantitative cross-species comparison and mechanistic investigation of both normal and pathological brain functions.

neuroscience↗

bioRxiv2025

Avoidance of fratricide and improved efficacy of CD33-MSLN CAR-iNK cells in treating acute myeloid leukemia

Acute myeloid leukemia (AML) patients are often older, which brings challenges of endurance and persistent efficacy of autologous CAR-T cell therapies. Allogenic CAR-NK cell therapies may offer reduced toxicities and enhanced anti-leukemic potential against AML. In this study, we designed a novel CD33-mesothelin loop CAR (Loop CAR) and evaluated its anti-tumor efficacy in human umbilical cord blood-derived NK (UCB-NK) cells and human pluripotent stem cell-derived NK (hPSC-iNK) cells. The Loop CAR exhibited superior cytotoxicity against dual-antigen-positive tumor cell lines and primary AML cells. To further avoid fratricide caused by endogenous CD33 expression in NK cells, we established a hPSC-derived cell line via knockout of CD33 gene (CD33KO) and engineered Loop CAR. Rather than enforced expression of exogenous CD16, we generated abundant mature CD33KO-Loop CAR-iNK cells highly expressing endogenous CD16 via an organoid induction approach. This innovative strategy effectively mitigated NK cell fratricide and significantly enhanced CD33 and mesothelin-mediated specific cytotoxicity. Moreover, the CD33KO-Loop CAR-iNK cells demonstrated superior tumor-killing activity in AML xenograft mice and significantly prolonged survival. hPSC-derived CD33KO-Loop CAR-iNK cells possess unique advantages and translational potential for treating AML.

cancer biology↗

bioRxiv2025

Engineered CRO-CD7 CAR-NK cells derived from pluripotent stem cells avoid fratricide and efficiently suppress human T-cell malignancies

BackgroundT cell malignancies are highly aggressive hematological tumors with limited effective treatment options. CAR-NK cell therapy targeting CD7 has emerged as a promising approach for treating T-cell malignancies. However, conventional CAR-NK cell therapy faces the challenges of cell fratricide due to CD7 expression on both malignant cells and normal NK cells. Additionally, engineering CARs into human tissue-derived NK cells demonstrates heterogeneity, low transduction efficiency, and high manufacturing costs. MethodsThe human pluripotent stem cells (hPSCs) were genetically modified by knocking out the CD7 gene and introducing the CD7 CAR expression cassette to generate CD7 KO-CD7 CAR-hPSCs. These modified hPSCs were subsequently differentiated into CD7 KO-CD7 CAR-iNK cells using an efficient organoid induction method. The cytotoxicity of CD7 KO-CD7 CAR-iNK cells against CD7+ tumor cells was evaluated. Furthermore, we overexpressed the CXCR4 gene in CD7 KO-CD7 CAR-hPSCs and derived CXCR4-expressing CD7 KO-CD7 CAR-iNK (CRO-CD7 CAR-iNK) cells. The dynamics of CRO-CD7 CAR-iNK cells in vivo were tracked, and their therapeutic efficacy was assessed using human T-cell acute lymphoblastic leukemia (T-ALL) xenograft models. ResultsThe CD7 KO-CD7 CAR-iNK cells derived from CD7 KO-CD7 CAR-hPSCs effectively avoided fratricide, demonstrated normal expansion, and exhibited potent and specific anti-tumor activity against CD7+ T-cell tumor cell lines and primary T-ALL cells. CXCR4 overexpression in CRO-CD7 CAR-iNK cells improved their homing capacity and extended their persistence in vivo. The CRO-CD7 CAR iNK cells significantly suppressed tumor growth and prolonged the survival of T-ALL tumor-bearing mice. ConclusionsOur study provides a reliable strategy for the large-scale generation of fratricide-resistant CD7 CAR-iNK cells with robust anti-tumor effects from hPSCs, offering a promising cell product to treat T-cell malignancy.

cancer biology↗

bioRxiv2025

WASTER: Practical de novo phylogenomics from low-coverage short reads

The advent of affordable whole-genome sequencing has spurred numerous large-scale projects aimed at inferring the tree of life, yet achieving a complete species-level phylogeny remains a distant goal due to significant costs and computational demands. Traditional species tree inference methods, though effective, are hampered by the need for high-coverage sequencing, high-quality genomic alignments, and extensive computational resources. To address these challenges, this study introduces WASTER, a novel de novo tool for inferring shallow phylogenies directly from short-read sequences. WASTER employs a k-mer based approach for identifying variable sites, circumventing the need for genome assembly and alignment. Using simulations, we demonstrate that WASTER achieves accuracy comparable to that of traditional alignment-based methods, even for low sequencing depth, and has substantially higher accuracy than other alignment-free methods. We validate WASTERs efficacy on real data, where it accurately reconstructs phylogenies of eukaryotic species with as low depth as 1.5X. WASTER provides a fast and efficient solution for phylogeny estimation in cases where genome assembly and/or alignment may bias analyses or is challenging, for example due to low sequencing depth. It also provides a method for generating guide trees for tree-based alignment algorithms. WASTERs ability to accurately estimate shallow phylogenies from low-coverage sequencing data without relying on assembly and alignment will lead to substantially reduced sequencing and computational costs in phylogenomic projects.

bioinformatics↗

bioRxiv2025

Smooth Muscle Cells and Fibroblasts in the Proximal Thoracic Aorta Exhibit Minor Differences Between Embryonic Origins in Angiotensin II-driven Transcriptional Alterations

BackgroundThoracic aortopathy is influenced by angiotensin II (AngII) and exhibits regional heterogeneity with the proximal region of the thoracic aorta being susceptible. Smooth muscle cells (SMCs) and selected fibroblasts in this region are derived from two embryonic origins: second heart field (SHF) and cardiac neural crest (CNC). While our previous study revealed a critical role of SHF-derived cells in AngII-mediated aortopathy formation, the contribution of CNC-derived cells remains unclear. MethodsMef2c-Cre R26RmT/mG mice were infused with AngII (1,000 ng/kg/min). Proximal thoracic aortas were harvested at baseline or after 3 days of infusion, representing the prepathological phase. Cells were sorted by origins using mGFP (SHF-derived) and mTomato (other origins, nSHF-derived) signals, respectively. After sorting cells by origin, single-cell RNA sequencing was performed and analyzed. ResultsShort-term AngII infusion induced significant transcriptomic changes in both SHF- and nSHF-derived SMCs, but differences between origins were modest. Fibroblast transcriptomes also underwent notable changes by AngII infusion, but differences between SHF and nSHF origins remained modest. Interestingly, AngII infusion resulted in the emergence of a new fibroblast sub-population. Several molecules related to the extracellular matrix, such as Eln and Col3a1, were downregulated in SHF-derived fibroblasts compared to nSHF-derived fibroblasts in the new subcluster. ConclusionFibroblasts in the new subcluster exhibited lineage-specific differences in extracellular matrix-related genes; however, overall transcriptomic differences between origins in SMCs and fibroblasts in response to AngII were modest in the pre-pathological phase of AngII-induced thoracic aortopathy. GRAPHIC ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=174 SRC="FIGDIR/small/610985v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@17c2e3corg.highwire.dtl.DTLVardef@1bf9517org.highwire.dtl.DTLVardef@d51aedorg.highwire.dtl.DTLVardef@dac951_HPS_FORMAT_FIGEXP M_FIG C_FIG

pathology↗

bioRxiv2025

Pyruvate and Related Energetic Metabolites Modulate Resilience Against High Genetic Risk for Glaucoma

A glaucoma polygenic risk score (PRS) can effectively identify disease risk, but some individuals with high PRS do not develop glaucoma. Factors contributing to this resilience remain unclear. Using 4,658 glaucoma cases and 113,040 controls in a cross-sectional study of the UK Biobank, we investigated whether plasma metabolites enhanced glaucoma prediction and if a metabolomic signature of resilience in high-genetic-risk individuals existed. Logistic regression models incorporating 168 NMR-based metabolites into PRS-based glaucoma assessments were developed, with multiple comparison corrections applied. While metabolites weakly predicted glaucoma (Area Under the Curve=0.579), they offered marginal prediction improvement in PRS-only-based models (P=0.004). We identified a metabolomic signature associated with resilience in the top glaucoma PRS decile, with elevated glycolysis-related metabolites--lactate (P=8.8E-12), pyruvate (P=1.9E-10), and citrate (P=0.02)--linked to reduced glaucoma prevalence. These metabolites combined significantly modified the PRS-glaucoma relationship (Pinteraction=0.011). Higher total resilience metabolite levels within the highest PRS quartile corresponded to lower glaucoma prevalence (Odds Ratiohighest vs. lowest total resilience metabolite quartile=0.71, 95% Confidence Interval=0.64-0.80). As pyruvate is a foundational metabolite linking glycolysis to tricarboxylic acid cycle metabolism and ATP generation, we pursued experimental validation for this putative resilience biomarker in a human-relevant Mus musculus glaucoma model. Dietary pyruvate mitigated elevated intraocular pressure (P=0.002) and optic nerve damage (P<0.0003) in Lmx1bV265D mice. These findings highlight the protective role of pyruvate-related metabolism against glaucoma and suggest potential avenues for therapeutic intervention.

genomics↗

bioRxiv2025

Light induces Phytochrome B SUMOylation to recruit the immune regulator NPR1 in nuclear condensates to control immunity in plants

It has long been observed that light perception by phytochromes control plant immunity, however, the underpinning molecular mechanism is less well understood. We demonstrate that light mediated SUMO conjugation to Phytochrome B (PhyB) is critical for increasing cellular salicylic-acid (SA) levels to orchestrate systemic acquired resistance (SAR) upon avirulent bacterial infection. SUMOylation is critical for PhyB nuclear condensate formation during light activated immunity. Light induced PhyB SUMOylation recruits NPR1, through its SUMO interacting motif to nuclear condensates to elevate SA levels for immune responses. In the dark during SAR, elevated SA levels substitute for light to maintain PhyB SUMOylation and immune-related photobody formation by stimulating the degradation of PhyB targeting deSUMOylase, OTS1. SUMOylated PhyB-NPR1 immune photobodies associate with TGA transcription factor associated chromatin to trigger immune gene expression. We unravel a mechanism where SUMOylation can enable light to recruit NPR1 to PhyB nuclear condensates to form immune photobodies to regulate plant immunity. HighlightsO_LILight-dependent immunity in plants relies on the SUMO mediated interaction between the photoreceptor PhyB and the Salicylic Acid (SA) receptor NPR1. C_LIO_LILight induced PhyB SUMOylation recruits NPR1 to nuclear condensates which we identify as immune photobodies that elevate SA levels for immune responses. C_LIO_LIIn darkness, SA can replace light in enabling PhyB-NPR1 immune photobody formation by regulating SUMOylation revealing a SA mediated mechanism for controlling PhyB liquid-liquid phase separation. C_LIO_LISUMO-modified PhyB-NPR1 immune photobodies regulate transcriptional activity of immune associated chromatin to shape defence responses in plants. C_LI

plant biology↗

bioRxiv2025

ca-circSCN8A promotes HPASMCs ferroptosis via LLPS initiated R-Loop

BACKGROUNDFerroptosis has been implicated in pulmonary hypertension. Chromatin-associated RNAs are linked to ferroptosis. However, their role in pulmonary vascular ferroptosis in PH is unexplored. METHODSBioinformatics, Sanger sequencing, RNase R and others were employed to identify differentially higher expression of ca-circSCN8A. Functional gain and loss assays were employed to unveil the role of ca-circSCN8A in hypoxia-induced redox-dependent ferroptosis in HPASMCs and PH mice model. Interaction between ca-circSCN8A and FUS was detected via RNA immunoprecipitation and pull-down assays. FRAP, CHIRP-qPCR, MDA, GSH and GSSG were conducted to explore the potential molecular mechanism. RESULTSca-circSCN8A was firstly identified and confirmed to be upregulated in PH. Upregulation of ca-circSCN8A can promote hypoxia induced ferroptosis in HPASMCs. Under hypoxic conditions, ca-circSCN8A promoted the lactylation of FUS by recruiting EP300, leading to formation of LLPS of ca-circSCN8A/FUS/EP300. LLPS maintained the stability of the R-Loop formed by ca-circSCN8A and ferroptosis related-gene SLC7A11 promoter that inhibit the transcription of the SLC7A11 gene, further result in the disruption of the redox balance and causes ferroptosis in HPASMCs. CONCLUSIONSca-circSCN8A recruits EP300 to promote the lactylation of FUS, thereby promoting LLPS formation of ca-circSCN8A/EP300/FUS. Further, the LLPS motivates ca-circSCN8A to form R-loop with its non-host SLC7A11 and participating in the regulation of hypoxic induced HPASMCs redox-dependent ferroptosis. This is the first confirmation that circRNAs forming R-loops with non-host genes regulated by LLPS. Our findings indicated that ca-circSCN8A plays an important role in ferroptosis of hypoxic induced HPASMCs and may be a potential target for the treatment of PH.

molecular biology↗

bioRxiv2025

Actomyosin and the Arp2/3 Complex Are Involved in the Internalization of Cellulose Synthase Complexes

The coupling of exo- and endocytic trafficking of Cellulose Synthase Complexes (CSCs) has been proposed to be important for maintaining the population of active CSCs at the plasma membrane (PM) and thus appropriate levels of cell wall assembly. Although actin and myosin are known to participate in the late stages of exocytosis of CSCs, their exact role during CSC internalization events remains controversial. We constructed a functional, photoconvertible fluorescent mEOS2-CESA6 reporter and developed single-particle live-cell imaging approaches to visualize and quantify the dynamic behavior of CSCs at the PM during internalization. Using the small molecule inhibitor of clathrin, Endosidin 9-17 or ES9-17, we confirmed that clathrin-mediated endocytosis is a major pathway for CSC internalization. We also found that the actin cytoskeleton is involved in CSC internalization. Genetic or chemical inhibition of actin, myosin, or the Arp2/3 complex significantly reduced the frequency of CSC internalization events and prolonged the CSC pause time prior to internalization. Additionally, we found that the Arp2/3 complex contributes to the late stage of exocytosis of CSCs into the PM. These results reveal a role for actomyosin and the Arp2/3 complex in both CSC secretion as well as internalization that was previously undescribed in plant cells. One sentence summaryDirect visualization of individual CSC internalization events reveals that actomyosin participates in CSC internalization and the Arp2/3 complex contributes to both exocytosis and internalization of CSCs through regulating the dynamic homeostasis of the cortical actin cytoskeleton.

cell biology↗

bioRxiv2025

Target-based de novo design of cyclic peptide binders

Cyclic peptides have become a new focus in drug discovery due to their ability to bind challenging targets, including "undruggable" protein-protein interactions, with low toxicity. Despite their potential, general methods for de novo design of cyclic peptide ligands based on target protein structures remain limited. Here, we developed CYC_BUILDER, a reinforcement learning based fragment growing method for efficient assembly of peptide fragments and cyclization to generate diverse cyclic peptide binders for target proteins. CYC_BUILDER employs a Monte Carlo Tree Search (MCTS) framework to integrate seed fragment exploration, fragment fusion based peptide growth, structure optimization, evaluation and peptide cyclization. It supports peptide cyclization through both head-to-tail amide bond and disulfide bond formation. We first validated CYC_BUILDER on known protein-cyclic peptide complexes, demonstrating its ability to accurately re-generate cyclic peptide binders in terms of both sequences and binding poses. We then applied it to design cyclic peptide inhibitors for TNF, a key mediator in inflammation-related diseases. Among the nine experimentally tested designed peptides, four showed potent binding to TNF and inhibited its cellular activity. CYC_BUILDER provides an efficient tool for cyclic peptide drug design, offering significant potential for addressing challenging therapeutical targets.

biochemistry↗

bioRxiv2025

Sequencing-based Spatial Transcriptomics with scRNA-seq Sensitivity

The advent of spatial transcriptomics has dramatically expanded our ability to study the vast network of cell-cell interactions at the molecular level in tissue. Among current methods, sequencing-based approaches have great potential in discovering because of its unbiased capture. In the last couple of years, the spatial resolution for the capture addresses has been significantly improved from 100 m to <1 m, well below the size of a mammalian cell. However, the capture efficiency has always been a pain point, [~]one order of magnitude lower than that of single cell RNA sequencing (scRNA-seq). The low capture efficiency limits the depth and breadth of its applications in the study of complex biological systems and diseases. Here, we introduce Salus Spatial transcriptomic system (Salus-STS), which provides [~]1 m capture resolution and a capture efficiency [~]1 order of magnitude higher than other current methods. Analysis with sub-cellular resolution becomes practical for sequencing-based spatial transcriptomics.

molecular biology↗

bioRxiv2025

Characterising the periodontal granulation tissue using scRNAseq.

AimsOur research investigated the cellular composition and molecular mechanisms of periodontal granulation tissue using single-cell RNA sequencing (scRNA-seq), aiming to enhance the understanding of periodontal disease pathogenesis and identify potential targets for regenerative therapies. Materials and MethodsGranulation tissue samples were collected from patients undergoing periodontal surgery. Fresh tissues were processed into single-cell suspensions and subjected to scRNA-seq. The data were integrated with existing datasets from healthy gingiva and periodontal ligament. Computational analyses were performed, and validation through immunofluorescence staining. ResultsTen distinct cell clusters were identified across the samples. Granulation tissue exhibited a higher abundance of immune cells compared to healthy tissues. A novel endothelial cell subpopulation, exclusive to granulation tissue, was discovered, characterized by NOTCH3 expression and involvement in ossification pathways. Additionally, granulation tissue Fibroblast subpopulations demonstrated a progenitor-like state, characterized by extracellular matrix reorganization and low differentiation, similar to cancer-associated fibroblasts. Conclusion(s)This study advances the understanding of periodontal disease by characterizing key regulatory cell populations within granulation tissue. The identification of the novel endothelial subpopulation offers new insights into the diseases pathogenesis and presents potential targets for regenerative therapies. These findings suggest opportunities for developing biomaterials that modulate specific cellular pathways to improve periodontal disease treatment.

cell biology↗

bioRxiv2025

Acquisition of discrete immune suppressive barriers contributes to the initiation and progression of preinvasive to invasive human lung cancer.

Computerized chest tomography (CT)-guided screening in populations at risk for lung cancer has increased the detection of preinvasive subsolid nodules, which progress to solid invasive adenocarcinoma. Despite the clinical significance, there is a lack of effective therapies for intercepting the progression of preinvasive to invasive adenocarcinoma. To uncover determinants of early disease emergence and progression, we used integrated single-cell approaches, including scRNA-seq, multiplexed imaging mass cytometry and spatial transcriptomics, to construct the first high-resolution map of the composition, lineage/functional states, developmental trajectories and multicellular crosstalk networks from microdissected non-solid (preinvasive) and solid compartments (invasive) of individual part-solid nodules. We found that early disease initiation and subsequent progression are associated with the evolution of immune-suppressive cellular phenotypes characterized by decreased cytotoxic CD8 T and NK cells, increased T cell exhaustion and accumulation of immunosuppressive regulatory T cells (Tregs) and M2-like macrophages expressing TREM2. Within Tregs, we identified a unique population of 4-1BB+ Treg subset enriched for the IL2-STAT5 suppressive pathway with transcription profiles supporting discrete metabolic alterations. Spatial analysis showed increased density of suppressive immune cells around tumor cells, increased exhaustion phenotype of both CD4 and CD8 T cells expressing chemokine CXCL13, and spatial micro-complex of endothelial and lymphocyte interactions within tertiary lymphoid structures. The single-cell architecture identifies determinants of early disease emergence and progression, which may be developed not only as diagnostic/prognostic biomarkers but also as targets for disease interception. Additionally, our dataset constitutes a valuable resource for the preinvasive lung cancer research community.

cancer biology↗

bioRxiv2024

The genetic diversity and populational specificity of the human gut virome at single nucleotide resolution

Large-scale characterization of gut viral genomes provides strain-resolved insights into host-microbe interactions. However, existing viral genomes are mainly derived from Western populations, limiting our understanding of global gut viral diversity and functional variations necessary for personalized medicine and addressing regional health disparities. Here, we introduce the Chinese Gut Viral Reference (CGVR) set, consisting of 120,568 viral genomes from 3,234 deeply sequenced fecal samples collected nationwide, covering 72,751 viral species-level clusters (VSCs), nearly 90% of which are absent from current databases. Analysis of single nucleotide variations (SNVs) in 233 globally prevalent VSCs revealed that 18.9% showed significant genetic stratification between Chinese and non-Chinese populations, potentially linked to bacterial infection susceptibility. The predicted bacterial hosts of population-stratified viruses exhibit distinct genetic components associated with health-related functions, including multidrug resistance. Additionally, viral strain diversity at the SNV level correlated with human phenotypic traits, such as age and gastrointestinal issues like constipation. Our analysis also indicates that the human gut bacteriome is specifically shaped by the virome, which mediates associations with human phenotypic traits. This foundational resource underscores the unique genetic makeup of the gut virome across populations and emphasizes the importance of recognizing gut viral genetic heterogeneity for deeper insights into regional health implications.

microbiology↗

bioRxiv2024

Enzyme-independent functions of HDAC3 in the adult heart

The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant ({Delta}33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2{beta} (LAP2{beta}). Tethering LAP2{beta} to the HDAC3 {Delta}33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

physiology↗

bioRxiv2024

Identification of SMARCA1 as a key regulator for Colorectal Cancer

Emerging evidence indicates that aberrations in the writing, reading, or erasure of chromatin modification codes are pivotal events in various human cancers. In this study, we conducted a systematic investigation of histone modification recognition proteins in a pair of colorectal cancer cell lines, SW480 and SW620. Using chromatin fractionation combined with data-independent acquisition mass spectrometry (DIA-MS), we developed a robust method to identify changes in histone modification recognition proteins during cancer progression. Our analysis revealed 22 proteins that were significantly upregulated and 22 proteins that were significantly downregulated in SW620 cells compared to SW480 cells. Notably, SMARCA1, a member of the ISWI family belonging to ATP-dependent chromatin remodeling complexes, was downregulated in SW620 cells compared to SW480 cells. Its high expression was strongly correlated with poor patient prognosis, aligning with the proposed role of SMARCA1 in promoting colorectal cancer (CRC) metastasis. Furthermore, reduced SMARCA1 expression altered the levels of metastasis-related matrix metalloproteinases (MMPs) in these cells. In conclusion, by systematically profiling histone modification recognition proteins in a matched pair of primary and metastatic CRC cell lines, we identified SMARCA1 as a potential driver of CRC metastasis and a promising therapeutic target for CRC patients.

cancer biology↗

bioRxiv2024

A Comprehensive Assessment of Methylation-Based Age Prediction Methods

DNA methylation (DNAm) clock is widely used to measure biological age, helping to identify key biomarkers associated with aging, infer the progression of aging, and have promise for elucidating, delaying, or even reversing aging. During the past decade, a large number of epigenetic clocks have been developed. However, they are decentralized, with applicable scopes overlapping. We benchmark 15 of these methods on 142 Illumina DNAm array datasets in five criteria and analyze the biological significance of CPGs about aging and overlapping. There are many exciting commons in models performance. We found the optimal model closely related to the numbers and characteristics of the training data. We provided a comprehensive assessment process to guide DNAm clock research at (https://dnamclock.com), the corresponding data and evaluation pipeline are freely available (https://github.comyNENUBioCompute/MethylationEvaluation), this study will aid in the development of improved tools designed to analyze increasingly large DNAm datasets.

bioinformatics↗