Biology subjects

Xie, G.

Publications and source records attributed to Xie, G..

At least 19 recordsLinked to original sources

bioRxiv2026

Genetic Variation, Iron Status, and FGF23 Signaling Converge to Regulate Renal Calcium Buffering in Sickle Cell Disease

Sickle cell disease (SCD) causes heterogeneous mineral imbalances including variable degrees of hypocalcemia. The kidney controls systemic calcium by reabsorbing calcium from the glomerular filtrate via paracellular transport and transcellular transport in the nephron tubules, yet it is unknown whether these processes are modulated by genetic or environmental factors or disrupted in SCD. Using SCD mouse models and single-cell multiomics, we identify the distal convoluted tubule (DCT) as the nephron segment most susceptible to calcium reabsorption dysfunction in SCD, mainly via reduction of calcium buffer protein calbindin 1 (CALB1). We show that CALB1 and its encoding mRNA are decreased in DCT cells in SCD, alongside decreased Klotho (KL)-dependent fibroblast growth factor (FGF) 23 signaling and intracellular calcium signaling. Dietary iron restriction reduces CALB1, KL, and calcium exporter SLC8A1 levels in SCD kidneys. Loss of CALB1 shifts DCT cells toward energy-inefficient glycolysis with the metabolite 2,3-diphosphoglycerate impairing KL-dependent FGF23 signaling to create a feed-forward loop suppressing calcium reabsorption. Analysis of gene expression and protein quantitative trait loci data from kidneys of genetically diverse mice revealed that Calb1 expression levels are highly heritable and co-regulated with Slc8a1, identifying a genetic axis that dictates differential capacities for calcium buffering and trafficking toward blood in the kidney. Together, these findings support a model in which genetic variation, dietary iron status, and FGF23 signaling converge on DCT calcium buffering to reduce renal calcium reabsorption in the SCD kidney. This points to personalized, genotype- and iron-dependent strategies for managing mineral metabolism in SCD patients.

physiology↗

bioRxiv2026

H3K4me3 recruits the chromatin remodeling DILL-PICKLE-PEPPERCORN complexes to promoters in plants

The plant CHD chromatin remodeler PICKLE (PKL) is a master regulator of cellular identity and differentiation, controlling developmental, hormonal and stress-response processes. Yet the molecular mechanisms underlying its function remain unclear. Here, we show that PKL forms three complexes, each composed of a protein of previously unknown function and one of three mutually exclusive novel DNAJ proteins that recruit HSP70-1. Simultaneous loss of all three DNAJs phenocopies the pkl mutant, indicating functional redundancy among PKL complexes. In vitro activity assays and cryo-electron microscopy reveal that PKL clamps nucleosomal DNA via its ATPase motor domain and recognizes H3K4me3 through its double chromodomain. Genome-wide profiling shows that H3K4me3 recognition positions PKL complexes at genic promoters to bidirectionally fine-tune gene expression. Together, these results provide structure-function insight into PKL recruitment and its control of developmental gene expression, and reveal a chaperone-coupled complex assembly that offers a broader perspective on how chaperone networks may support chromatin remodeling complexes across eukaryotes.

plant biology↗

bioRxiv2026

Rescue schizophrenia-related phenotypes caused by Setd1a deficiency by histone demethylase inhibitors

Schizophrenia (SCZ) is a genetically complex neuropsychiatric disorder in which rare loss-of-function mutations in the histone methyltransferase SETD1A confer substantial risk. Although SETD1A haploinsufficiency had been linked to morphological, synaptic and behavioral abnormalities in the prefrontal cortex, whether and how SETD1A coordinates transcriptional and functional programs across different brain regions remains unknown. Here, we delineate the brain region-specific effects of SETD1A-associated dysfunction using conditional Setd1a knockout mice. We find that the dorsal striatum (dStr) and mediodorsal thalamus (MD) exhibit distinct transcriptomic and neuronal alterations to those in the PFC, and show transcriptomic enrichment for other SCZ risk genes. Loss of Setd1a in the dStr or MD drives selective vulnerability in key behavioral assays, suggesting important roles for these brain regions in the etiology of SCZ. By screening 6 existing H3K4 demethylase inhibitors, we identify the LSD1 (KDM1A) inhibitor TAK-418 as a potent modulator capable of restoring H3K4me3 levels and gene expression, as well as rescuing synaptic and SCZ-like behavioral phenotypes in the Setd1a+/- mice. Thus, our work provides a mechanistic link between high-penetrance SETD1A variants and region-specific brain dysfunction, establishing a framework for connecting rare loss-of-function variation in chromatin regulators to multidimensional neuropsychiatric phenotypes.

neuroscience↗

bioRxiv2026

Spatially resolved cellular and circuit architecture of the insular cortex controlling different dimensions of pain

Chronic pain is a leading cause of human suffering, affecting about 20% of the population. The insular cortex (IC) is a central hub for the multidimensional experience of pain, yet how the diverse neurons in IC are organized and assembled into functional circuits remains unclear. Here, combining multiplexed error-robust fluorescence in situ hybridization (MERFISH), neural tracing and in vivo functional analyses, we resolve the molecular, cellular and circuit architecture of the IC. We find that neuronal projections are specified by both transcriptomic identity and spatial topography. We further show that three molecularly defined neuron types in the posterior IC form discrete brain-wide networks that differentially regulate pain. Layer 5 pyramidal tract (PT) neurons regulate mechanical, thermal and affective pain. In contrast, layer 5 intratelencephalic (IT) neurons selectively modulate thermal nociception, whereas layer 6 corticothalamic (CT) neurons surprisingly relieve negative pain affects. Together, these findings reveal the spatially resolved cellular and circuit organization of the IC governing different dimensions of pain and uncover targets for precision pain therapy.

neuroscience↗

bioRxiv2026

MLL3 adaptor function, not methyltransferase catalytic activity, is essential for breast tumor suppression

MLL3 (Mixed-Lineage Leukemia 3), also known as KMT2C, is one of the most frequently altered epigenetic regulators in breast cancer. MLL3 loss-of-function leads to accelerated tumor onset and growth and increased metastasis. As a large multi-domain protein, MLL3 functions as a histone methyltransferase and a nuclear protein adaptor interacting with other epigenetic proteins. Since breast cancer MLL3 mutations are often truncating mutations that lead to protein degradation, whether the MLL3 tumor suppressor activity depends on its catalytic activity or non-catalytic chromatin adaptor function remains unclear. Here, using CRISPR genetically engineered mouse mammary stem cell organoid-based breast tumor models, we dissected dosage-dependent and domain-specific functions of MLL3 in breast tumor suppression. MLL3 heterozygous loss breast tumor models revealed that MLL3 is haplo-insufficient for breast tumor suppression. Interestingly, homozygous catalytic-dead MLL3-Y4792A mutation did not accelerate tumor onset, growth, or metastasis. By contrast, G367V mutation in the PHD2 domain, which disrupts the BAP1 complex binding without affecting MLL3 protein stability, accelerated tumor onset and growth, phenocopying MLL3 loss. Mechanistically, MLL3 loss impaired chromatin localization of UTX, and genetic depletion of UTX accelerated breast tumor progression in MLL3-wildtype but not MLL3-deficient cells. Integrated RNA-seq, CUT&TAG, and ATAC-seq analyses further showed that transcriptional changes induced by MLL3 loss were more closely associated with promoter-proximal alterations in H3K27Ac, H3K27me3, and chromatin accessibility than with putative MLL3-dependent enhancer regions. Together, these findings reveal that MLL3 suppresses breast tumor initiation through a dosage-sensitive, catalytic-independent adaptor function that regulates promoter-proximal epigenetic states.

cancer biology↗

bioRxiv2026

Toward CT-based Tractography: Presurgical White Matter Tract Mapping in Intracerebral Hemorrhage

Presurgical mapping of key white matter (WM) fiber tracts is crucial for intracerebral hemorrhage (ICH) surgery, but it currently relies on tractography from diffusion MRI (dMRI), which has limited applicability in urgent or resource-constrained settings due to long scan times and limited MRI availability. To bridge this gap, we developed a deep learning approach designed to reconstruct critical fiber tracts directly from routinely acquired CT scans, focusing on the corticospinal tract (CST) due to its high clinical relevance. By training a novel network on a curated dataset of 150 paired CT-dMRI scans (101 ICH patients and 49 healthy subjects), we enabled the direct mapping of the CST from CT images alone, bypassing the traditional requirement for dMRI. Our results demonstrate that the CT-derived tracts achieve high anatomical plausibility, with neurosurgeon expert assessments yielding a Likert score of 3.64. Furthermore, the clinical relevance of these reconstructions was validated by a significant correlation between CT-derived tract integrity and patient motor scores (r = 0.726, p = 3.731x 10-7). These findings suggest that in complex clinical scenarios, particularly where dMRI signal quality is compromised by lesion-induced distortion, this CT-based mapping may serve as a useful anatomical reference. Overall, by enabling CT-based WM mapping, our method potentially offers a practical route to gain the key advantages of tractography in resource-limited or time-critical settings

neuroscience↗

bioRxiv2026

Decoding heterogeneous aging clocks and disease risk stratification using a metabolomic foundation model

Metabolomic aging clocks estimate biological age by modeling metabolite concentrations, thereby capturing aging signals from healthspan and adverse outcomes. However, existing clocks generally assume homogeneous aging trajectories and yield only a single age acceleration metric, limiting their capacity to capture inter-individual metabolic heterogeneity and characterize nuanced individual-level representations. To address these limitations, we proposed MetAgeFormer, a transformer-based metabolomic model pre-trained on nuclear magnetic resonance (NMR) metabolomic profiles from over 430,000 participants in UK Biobank via self-supervised learning. This large-scale pre-training enables MetAgeFormer to learn a metabolomic representation space that captures the complex, nonlinear structure of systemic metabolism as reflected in NMR data. Building on MetAgeFormer, we developed a mortality-informed metabolomic aging clock by fine-tuning an attached survival module, deriving age acceleration that demonstrates significant associations with multiple age-related diseases and factors. We further validated zero-shot transfer in the independent Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. More importantly, we utilized embeddings generated by MetAgeFormer to identify 13 distinct metabolic subtypes and consolidated them into four meta-subtypes with markedly divergent susceptibility profiles for major age-related diseases, particularly type 2 diabetes and neurodegenerative disorders. This finding empirically demonstrated substantial metabolic heterogeneity across populations, persisting even at comparable levels of age acceleration. To enhance clinical applicability, we further employed contrastive learning to distill a lightweight model that approximates the learned metabolomic representation space using only 14 routine clinical blood test measurements as inputs. Both hold-out testing within UK Biobank and external validation in the China Health and Retirement Longitudinal Study replicated similar disease onset patterns across the identified subtypes, underscoring the robust generalizability of MetAgeFormer and supporting its translational potential as a scalable framework for metabolomic aging assessment and early disease risk stratification.

bioinformatics↗

bioRxiv2026

Microglia-derived IL-18 remodels hippocampal plasticity to constrain traumatic fear memory

Post-traumatic stress disorder (PTSD) involves complex neuroimmune-synaptic crosstalk in the hippocampus. Here we show that interleukin-18 (IL-18), an extensively studied pro-inflammatory cytokine, serves a protective role against traumatic fear memory through a microglia-to-neuron signaling axis. Traumatic stress induces sustained upregulation of IL-18 in the hippocampus. Exogenous IL-18 administration attenuates fear memory, whereas blockade of IL-18 signaling exacerbates it. Mechanistically, microglial-derived IL-18 acts on neuronal IL-18R1 to restore stress-impaired synaptic plasticity and reduce perineuronal net density, thereby facilitating structural synaptic remodeling. In addition, IL-18 modulates the synaptic organization of fear memory-encoding engram cells within hippocampal ensembles. Together, these findings redefine IL-18 as a homeostatic regulator of post-trauma hippocampal synaptic function and identify the hippocampal IL-18 pathway as a potential therapeutic target for PTSD.

neuroscience↗

bioRxiv2026

Chromatin landscape and epigenetic heterogeneity of acute myeloid leukemia

Acute myeloid leukemia (AML) is an aggressive hematologic cancer characterized by proliferation of immature myeloblasts. It shows profound molecular heterogeneity, which has been primarily studied through genetic abnormalities, providing the basis for disease classification, prognostication, and therapeutic choice. However, genetic factors alone may not fully explain AML pathogenesis and diversity, while leaving the role of abnormal epigenome, particularly chromatin state, largely unexplored in a large cohort of patients. Here we show that AML is classified into 16 subgroups with distinct chromatin accessibility profiles based on ATAC-seq in 1,563 AML cases, including novel AML subgroups not previously recognized in conventional genomic classifications. By integrating multi-omics analyses of genome, transcriptome, and major histone marks, we show that these epigenetic subgroups exhibit unique features in clinical presentation, gene mutations, differentiation states, gene expression, and super-enhancer profiles, which are validated across independent cohorts. Single-cell sequencing demonstrates the presence of subgroup-specific ATAC signatures that are shared by all leukemic cells, confirming the definitive role of the epigenome in the ATAC-based classification. Mechanistically, each subgroup is associated with a distinct gene regulatory network centered on key transcription factors, where subgroup-specific super-enhancers play a pivotal role. These ATAC subgroups also have prognostic significance independent of genomic classification, and help reveal unexpected drug sensitivities. In summary, ATAC-based chromatin profiling in this large sample set, combined with multi-omics data, provides new insights into AML pathogenesis beyond genomic profiling and also serves as an invaluable resource for AML research.

cancer biology↗

bioRxiv2026

Histone methylation activity of KMT2D is required for proliferative control of the developing lung

KMT2D, the histone methyltransferase and core component of the COMPASS/MLL4 complex, has been implicated in developmental diseases such as Kabuki Syndrome, interstitial lung disease, and congenital diaphragmatic hernia, with clear links to pediatric pulmonary disorders. Despite this, the mechanism by which KMT2D governs lung development remains unclear. Knock-in mouse models rendering, KMT2D catalytically deactivated (KMT2DKI) and reducing H3K4 methylation, have demonstrated potential in defining KMT2Ds role in pulmonary development. Our examination of the lungs of KMT2DKI mice revealed increased cellular density and impaired sacculation indicated by reduced airspace chord length, thickening of intersaccular septa, and abnormal alveolar cell differentiation. KMT2DKI mice revealed narrowed Sox2+ conducting airways and epithelial differentiation defects characterized by reduced Cc10+ club cells. Accompanying the alveolar and airway hypoplasia, blood vessel luminal area was reduced. Conversely, KMT2DKI lungs had a significantly higher proportion of proliferating cells accompanied by a dramatic expansion in Pdgfr+ mesenchymal progenitor cells. Our findings therefore suggest that KMT2D-mediated H3K4 methylation is vital to normal lung development, and its impairment results in widespread pulmonary hypoplasia and potentially pulmonary hypertension.

developmental biology↗

bioRxiv2025

MLL3 and MLL4 sustain hematopoietic stem cell multipotency by opposing a B-cell default state

Hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) are sustained by networks of transcription factors and epigenetic regulators that prime lineage-specific programs yet maintain multipotency. Two epigenetic regulators, MLL3 and MLL4, play important but opposing roles in maintaining this balance. MLL3 promotes HSC differentiation, whereas MLL4 opposes differentiation. These opposing functions are essential for both normal homeostasis and leukemia suppression, yet it is not clear how MLL3 and MLL4 regulate HSC and MPP gene expression to control HSC/MPP fate decisions. To resolve these mechanisms, we performed an extensive series of single cell genomic studies after conditionally deleting Mll3, Mll4 or both genes together. Mll3 deletion had only limited effects on HSC/MPP enhancer networks at steady state, whereas Mll4 deletion led to precocious activation of myeloid enhancers. Surprisingly, compound Mll3/4 deletion eliminated all myeloid, erythroid and megakaryocytic potential within the hematopoietic hierarchy and caused all progenitors to rapidly default to a B-cell-like identity. These changes were accompanied by widespread inactivation of HSC/MPP enhancers and superenhancers, and ectopic activation of B-cell superenhancers. Disabling MLL3/4 histone methyltransferase activity did not recapitulate the pervasive changes in cell identity that were observed when MLL3 and MLL4 were fully inactivated, indicating that MLL3 and MLL4 activate HSC/MPP enhancers independently from their enzymatic activities. Our findings show that HSC/MPP multipotency requires sustained tension between MLL3/4-dependent enhancers that maintain myeloid, erythroid and megakaryocyte potential, and MLL3/4-independent enhancers that prime B-cell identity. MLL3 and MLL4 therefore serve as critical linchpins of multilineage hematopoiesis. KEY POINTSO_LIMLL3 and MLL4 act redundantly in HSCs to sustain transcription factor and enhancer networks that support multipotency C_LIO_LISimultaneous loss of MLL3 and MLL4 drives hematopoietic progenitors into a uniform B-cell-like default state C_LI

cell biology↗

bioRxiv2025

scAgeClock: a single-cell transcriptome based human aging clock model using gated multi-head attention neural networks

Aging Clock models have emerged as a crucial tool for measuring biological age, with significant implications for anti-aging interventions and disease risk assessment. However, human aging clock models that offer single-cell resolution and account for cell and tissue heterogeneities remain underdeveloped. This study introduces scAgeClock, a novel gated multi-head attention (GMA) neural network-based single-cell aging clock model. Leveraging a large-scale dataset of over 16 million single-cell transcriptome profiles from more than 40 human tissues and 400 cell types, scAgeClock demonstrates improved age prediction accuracy compared to baseline methods. Notably, the mean absolute error for the best-performing cell type is remarkably low at 2 years. Feature importance analysis reveals enrichment of aging clock genes related to ribosome, translation, defense response, viral life cycle, programmed cell death, and COVID-19 disease. A novel metric, the Aging Deviation Index (ADI) proposed by this study, revealed deceleration of ages in cells with higher differentiation potencies and tumor cells in higher phases or under metastasis, while acceleration of ages was observed in skin cells. Furthermore, scAgeClock is publicly available to facilitate future research and potential implementations.

bioinformatics↗

bioRxiv2025

A molecularly defined basalo-prefrontal-thalamic circuit regulates sensory and affective dimensions of pain

Both the medial prefrontal cortex (mPFC) and thalamus have been implicated in pain regulation. However, the roles of the mPFC-thalamus connection in pain and how the mPFC modulates nociceptive processing remain unclear. Here, we show that the mPFC neurons projecting to thalamus, marked by Foxp2 expression, are deactivated in both acute and chronic pain in male mice. Persistent inactivation of the mPFC Foxp2+ neurons enhances nociceptive sensitivity, while their activation alleviates multiple aspects of pain. Circuit-specific manipulations revealed that the projections to parataenial nucleus, mediodorsal and ventromedial thalamus differentially modulate sensory and affective pain. Additionally, the mPFC Foxp2+ neurons receive cholinergic input from the basal forebrain, particularly the horizonal diagonal band (HDB). Notably, activation of the 4{beta}2-containing nicotinic acetylcholine receptor in mPFC exerts antinociceptive effects in Foxp2+ neuron-dependent manner. Together, our study defines an HDB[->]mPFCFoxp2[->]thalamus circuit essential for sensory and affective pain modulation and underscores the therapeutic potential of targeting mPFC cholinergic signaling in chronic pain management.

neuroscience↗

bioRxiv2025

TIP-seq: A Single-cell Multiomics Approach for Simultaneous Transcriptome and Intracellular Protein Profiling

Single-cell multiomics technologies have significantly advanced our understanding of cellular heterogeneity; however, the concurrent profiling of mRNA transcripts and target proteins continues to pose a substantial challenge. To bridge the gap between single-cell sequencing and proteomic methods, we developed an innovative single-cell multiomics methodology, termed TIP-seq, which facilitates the simultaneous profiling of the transcriptome and intracellular proteins without prior cell manipulation. In TIP-seq, microfluidic technology is leveraged to integrate oligonucleotide-labeled antibodies with hydrogel beads, allowing for the capture of mRNAs and proteins from individual cells within droplets, thereby enabling high-throughput and precise dual-omics data acquisition. When applied to lung cell lines and non-small cell lung cancer (NSCLC) tissues, TIP-seq analysis revealed notable cellular heterogeneity and molecular dynamics, emphasizing the distinct immune cell interactions within NSCLC tissues. Key immune checkpoint interactions in NSCLC, such as SPP1-CD44, NECTIN2-TIGIT, and NECTIN2-CTLA4, along with functional alterations in tumor-associated dendritic cells (DCs) and T cells, were identified via TIP-seq, underscoring their pivotal roles in mediating immune suppression within the tumor microenvironment. Collectively, TIP-seq represents a powerful methodology for identifying novel therapeutic targets and biomarkers, thereby holding significant potential for the advancement of precision medicine in the treatment of lung cancer and other complex diseases.

biochemistry↗

bioRxiv2025

Longitudinal and large-scale monitoring of transcriptome and RBP-RNA interactome in living cells by engineered protein nanocages

Nondestructive sequencing of RNA from live cells is essential for monitoring and understanding dynamic biological processes. However, most existing RNA sequencing methods rely on cell lysis or fixation, limiting their applicability for longitudinal studies. Here, we introduce POND-seq (Protein nanocage-empOwered Non-Destructive sequencing), a novel approach that employs secretory protein nanocages fused with RNA-binding proteins (RBPs) to capture the RBP-RNA interactome and transcriptome in live cells. POND-seq reliably identifies RNA targets of canonical RBPs across multiple cell types. By fusing poly(A)-binding protein (PABPC1) to the nanocage, we demonstrate that POND-seq can monitor transcriptomic changes in response to signaling stimuli and selectively capture cell-type-specific transcriptomes from mixed populations. Additionally, POND-seq facilitates the dissection of RNA-binding domains and key amino acid residues critical for RBP-RNA interactions. We further highlight its utility in large-scale screening, offering compelling evidence for the pathogenicity of FMR1 variants. POND-seq represents a transformative advancement in RNA biology, cell biology and precision medicine, enabling unprecedented insights into cellular dynamics and disease mechanisms.

molecular biology↗

bioRxiv2024

Rotational migration in human pancreatic ductal organoids depends on actin and myosin activity

Rotational migration is one specific form of collective cell migration when epithelial cells are confined in a spherical geometry, such as in the epithelial acini. This tissue-level rotation motion is crucial for the morphogenesis of multiple epithelial systems. Here, we introduce a new primary human model for the study of rotational migration, pancreatic ductal organoids. Live imaging revealed the persistent rotation of the organoids over time. By tracking the nuclei, the three-dimensional trajectory of the cellular movement was reconstructed and the velocity of the rotation was quantified. The presence of focal adhesion clusters and prominent actin stress fibers were observed at the basal side of the organoids, suggesting the interactions between the cells and the surrounding extracellular matrix. Finally, our inhibition study showed the dependence of pancreatic ductal organoid rotational migration on myosin activity, actin polymerization, and actin branching. We hope that this model will enable future studies with human primary cells, which are more faithful to normal epithelial cells.

cell biology↗

bioRxiv2024

Universal features of Alternative splicing in response to diverse environmental stimuli in rice and the vital roles of TFs in AS regulation

BackgroundPre-mRNA alternative splicing (AS) plays essential roles in response to environmental stimuli in plants. However, the universal and specific features of splicing in response to diverse environmental conditions remain not fully understood. Recent studies have shown the co-transcriptional characteristics of splicing, which lead to the reasonable speculation that the elements or factors regulating transcription can also affect splicing. Among of which, the effects of transcription factors on alternative splicing in plants under environmental stimuli are still confusing. A large amount 0f public available RNA sequencing data are valuable resources to be re-analyzed for answering questions beyond the aims of their original studies. ResultsWe explored the universal features of AS using a standard RNA-seq dataset TENOR, which stems from rice samples under controlled diverse conditions to provide comprehensive and comparable AS analysis under various conditions. We found that AS widely occurs in rice under stimuli, with significant tissue specificity, temporal dynamics, commonality among different stresses or treatments as well as significant difference between differential alternative splicing and expressed genes (DASGs and DEGs) in rice under environmental stimuli. The majority of DASGs under various stresses are splicing factors and transcription factors. The correlation analysis shows that the expression level of transcription factors is significantly correlated with the PSI of AS events. The predominant transcription factors correlating with alternative splicing events come from bHLH, bzip and hsfa families. We validated the effects of transcription factors on AS by analyzing RNA-seq data from transcription factor mutants and found substantial differential AS events between mutants and wild type. Furthermore, the significant correlation was discovered between the transcription levels of transcription factors and splicing factors. ConclusionWe found universal features of AS and the predominant AS events of SFs and TFs in plants under diverse environments. We propose that TFs might regulated AS of download genes partly by changing the patterns of their own transcription and splicing to further regulate the transcription of SFs. This work illuminate the studies on the possible mechanisms by which TFs modulate AS in plant, especially under environmental stimuli.

plant biology↗

bioRxiv2024

Cost-effective DNA storage with DNA movable type

In the face of exponential data growth, DNA-based storage offers a promising solution for preserving big-data. However, most existing DNA storage methods, akin to traditional block printing, require costly chemical synthesis for each individual data file, adopting a sequential, one-time-use synthesis approach. To overcome these limitations, we introduce a novel, cost-effective "DNA-Movable-Type Storage" system, inspired by movable type printing. This system utilizes pre-fabricated DNA movable types-short, double-stranded DNA oligonucleotides encoding specific payload, address, and checksum data. These DNA-MTs are enzymatically ligated/assembled into cohesive sequences, termed "DNA movable type blocks", streamlining the assembly process with the automated BISHENG-1 DNA-MT inkjet printer. Using BISHENG-1, we successfully printed, assembled, stored and accurately retrieved 43.7 KB of data files in diverse formats (text, image, audio, and video) in vitro and in vivo, using only 350 DNA-MTs. Notably, each DNA-MT, synthesized once (2 OD), can be used up to 10,000 times, reducing costs to 122 $/MB-outperforming existing DNA storage methods. This innovation circumvents the need to synthesize entire DNA sequences encoding files from scratch, offering significant cost and efficiency advantages. Furthermore, it has considerable untapped potential to advance a robust DNA storage system, better meeting the extensive data storage demands of the big-data era.

bioinformatics↗