Biology subjects

Tian, Y.

Publications and source records attributed to Tian, Y..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

LARP4 is a B cell-specific metabolic checkpoint for plasma cell differentiation and a therapeutic target in systemic lupus erythematosus

RNA-binding protein LARP4 plays an important role in T cell activation and differentiation, but its role in B cell biology and the pathogenesis of systemic lupus erythematosus (SLE) remains unclear. This study found that LARP4 was specifically highly expressed in B cells of SLE patients and was positively correlated with disease activity. By constructing T cell-specific and B cell-specific conditional knockout mice, we found that deletion of LARP4 in B cells, but not in T cells, significantly alleviated pristane-induced and Bm12-induced lupus nephritis. Further analysis showed that LARP4 deletion selectively inhibited B cell differentiation into plasma cells, but did not affect germinal center B cell formation. Integrated transcriptomic and metabolomics analyses revealed that this effect is due to reduced phosphatidic acid synthesis and decreased mTORC1 activity caused by mitochondrial oxidative phosphorylation dysfunction. Furthermore, we used LIPEP, a LARP4 inhibitory peptide that effectively mimicked the therapeutic effects of LARP4 gene knockout in the MRL/lpr spontaneous lupus model and outperformed cyclophosphamide in reducing glomerular immune complex deposition and improving extrarenal dermatitis. These results indicates that LARP4 is a key metabolic checkpoint regulating B cell differentiation into Plasma cells and suggest that it may be a potential therapeutic target for SLE.

immunology↗

bioRxiv2026

nanoASM: Long-Read Allele-Specific DNA Methylation Profiling Enables Functional Annotation of Regulatory Noncoding Variants in Human Prostate Tissues

Long-read nanopore sequencing enables simultaneous detection of germline variation and native DNA base modifications on individual DNA molecules, providing a unique opportunity to investigate allele-specific epigenetic regulation. Here, we performed whole-genome nanopore sequencing on normal and tumor prostate tissues to characterize differential methylation, methylation entropy, and allele-specific methylation (ASM) associated with noncoding genetic variants. Genome-wide analysis identified extensive cancer-associated differentially methylated regions (DMRs), with hypermethylated DMRs significantly enriched near transcription start sites and transcriptional regulatory regions. Integration with transcriptomic datasets revealed strong inverse relationships between promoter methylation and gene expression, while 5-hydroxymethylcytosine (5hmC) levels positively correlated with transcriptional activity across gene bodies. Using fragment-level methylation patterns enabled by long-read sequencing, we further quantified methylation entropy incorporating both 5mCG and 5hmCG states. Cancer-hypermethylated DMRs exhibited markedly reduced entropy, consistent with clonal fixation of methylation states during tumor progression. Entropy profiling across chromatin annotations demonstrated maximal epigenetic heterogeneity at partially modified enhancer-associated regions. To investigate cis-regulatory genetic effects, we developed a simple ASM framework (nanoASM) that can partition sequencing reads by allelic state and identifies allele-specific DMRs directly from long-read data. Compared with conventional population-level mQTL analysis, ASM demonstrated substantially improved statistical efficiency by leveraging within-individual contrasts and reducing sample-level heterogeneity. Although germline single nucleotide polymorphisms (SNPs) were largely shared between normal and tumor tissues, ASM patterns differed substantially, with tumor-associated ASM regions displaying significantly larger genomic span and stronger allelic methylation differences. Comparative analysis with TCGA prostate mQTL and GTEx prostate eQTL datasets demonstrated substantial concordance between ASM directionality and downstream transcriptional effects, particularly for variants located within DMRs and near transcription start sites. At the IRX4 prostate cancer risk locus, ASM identified an androgen-responsive regulatory domain overlapping AR ChIP-seq and H3K27ac peaks, nominating rs6885084 as a candidate functional variant. At the PSCA locus, ASM anchored by rs4736369 was associated with allele-specific methylation, chromatin activation, transcript abundance, and isoform usage. Together, these findings establish nanopore-based ASM analysis as a powerful approach for resolving functional noncoding variants and their regulatory domains they control in prostate cancer.

genetics↗

bioRxiv2026

Systematic Quantitative Proteomics Defines Age, Sex, and Region-Dependent Remodeling of Lung Extracellular Matrix

The lung extracellular matrix (ECM) governs tissue architecture, mechanics, and function, yet how it remodels with age across sex and anatomical regions remains poorly understood. Here, we performed a systematic multi-factor proteomic analysis of rat lungs to define age-, sex-, and region-dependent remodeling across the tissue landscape. Age emerged as the dominant source of variation, with a conserved aging signature modified by region- and sex-specific effects. Young lungs showed coordinated ECM assembly, balanced proteolysis, and active biosynthetic programs consistent with structural adaptability and mechanical resilience. In contrast, aged lungs exhibited accumulation of mature collagen crosslinks and a more stabilized matrix architecture, indicating progressive matrix maturation and reduced structural plasticity. These changes were accompanied by proteomic signatures of metabolic stress and immune activation, suggesting coordinated remodeling across ECM, metabolic, and immune pathways during lung aging. Aging effects varied across anatomical regions and were more pronounced in females, highlighting context-dependent trajectories within the broader aging program. Age also partially reshaped spatial proteomic heterogeneity across lung compartments. Together, these findings identify matrix stabilization as a central feature of lung aging that links structural remodeling to metabolic-inflammatory imbalance and increased pulmonary vulnerability.

biochemistry↗

bioRxiv2026

A multimodal foundation model linking histopathology and DNA methylation

Hematoxylin and eosin (H&E) slides are routinely available in cancer care, but molecular profiling often requires additional tissue processing and turnaround time. We introduce HistoMethyl, a DNA methylation-aware pathology foundation model that aligns whole-slide histopathology with matched genome-scale methylation beta-value profiles during pre-training while requiring only an H&E slide at inference. We evaluated HistoMethyl across four task groups: gene mutation prediction, morphology-associated classification, overall survival prediction, and direct DNA methylation beta-value recovery. Evaluation spanned TCGA cross-validation, a disease-held-out lower-grade glioma cohort, and external cohort validation in CPTAC glioblastoma and SurGen rectal adenocarcinoma, totaling 14 cancer cohorts and 81 gene mutation tasks. The best-performing configuration improved mean mutation AUROC by 5.03 percentage points. By converting DNA methylation supervision into an H&E-only representation, His-toMethyl could support an early molecular triage layer that helps prioritize cases for confirmatory sequencing, methylation profiling, immunohistochemistry, and molecular tumor board review. These image-only predictions are intended to accelerate downstream molecular testing and tissue allocation while leaving final diagnosis and treatment selection anchored in validated molecular assays.

Cancer Biology↗

bioRxiv2026

Comprehensive Complete-Genome Analysis of Lactobacillaceae and Bifidobacteriaceae Reveals Strain-Specific Metabolic Interactions in Chinese Gut Microbiota

Bifidobacteriaceae and Lactobacillaceae are key probiotic families and widely used in food production, yet a comprehensive understanding of strain functions and their gut microbial interactions based on complete genomes remain understudied. Here we constructed a complete-genome dataset of 3,300 strains from these two families, including 1,151 newly isolated from China. Compared with draft assemblies, complete genomes substantially recovered a gene functional landscape encompassing stress tolerance, surface exopolysaccharide synthesis, nutrient utilization, and mobile genetic elements. Major species from both families exhibited a prevalence >60% in the Chinese population, far higher than that in US/Dutch cohorts. Notably, as a core probiotic species with remarkable genomic plasticity and gut-adaptive potential, Lactiplantibacillus plantarum stood out in our dataset for its enriched functional profile and was particularly abundant in the Chinese population. Moreover, compared with non-Chinese genomes, our isolates of key species displayed less metabolic complementarity and stronger competition with potentially pathogenic keystone species in the gut, thereby linking strain origin to enhanced probiotic potential and ecological fitness to benefit human gut health.

microbiology↗

bioRxiv2026

Spikes meet Spins: Quantum-Native Neural Decoding for Ultra_Low-Latency Brain-Computer Interfaces

Brain - computer interfaces (BCIs) require rapid and accurate decoding of neural activity, yet conventional computing architectures face growing latency as neural recording scales. We demonstrate a quantum computing - enabled neural decoding approach using a physical 1000-qubit coherent photonic Ising machine, in which inference is performed through hardware energy relaxation rather than numerical computation. By mapping sparse neural spike patterns onto Ising Hamiltonians, our hardware-native Quantum Semi-Restricted Boltzmann Machine achieves up to 96.2% accuracy across public in vivo datasets spanning multiple species and modalities. We report hardware-verified median latencies of 0.075 ms-- a tenfold speedup over GPUs--with complexity-invariant scaling. These results establish quantum computing as a viable pathway toward ultra-low-latency neural decoding for future BCI systems.

neuroscience↗

bioRxiv2026

Cryo-EM elucidation of stoichiometric plasticity, asymmetric ligand recognition and allosteric coupling in human P2X2/3 heterotrimeric channels

P2X receptors are trimeric ATP-gated ion channels that assemble as homo- or heterotrimers, with heteromeric forms exhibiting intrinsic asymmetry that influences function. Here, we report four high-resolution cryo-EM structures of human P2X2/3 heterotrimers representing distinct functional states, including ATP-bound assemblies (P2X332 and P2X223), the apo form, and a ligand/ATP-bound closed conformation. The three ATP-binding sites show asymmetric recognition of MgATP{superscript 2}- and ATP-, and channel activation requires occupancy of only two MgATP{superscript 2}- molecules. Gefapixant binds a single allosteric site and selectively inhibits MgATP{superscript 2}-, but not ATP-, binding, indicating orthosteric-allosteric coupling within the heterotrimer. Structural features of the transmembrane domain define ion permeation, particularly for Ca{superscript 2}. Despite asymmetric ligand interactions, gating remains largely symmetric, with minor differences in desensitization. These findings provide a structural framework linking asymmetry to coordinated channel function and open avenues for subtype-selective therapeutic intervention.

biophysics↗

bioRxiv2026

Celastrol alleviates SGLT2 inhibitor-induced diabetic hyperketonemia by inhibiting hepatic ketogenesis

SGLT2 inhibitor (SGLT2i)-induced diabetic hyperketonemia is a life-threatening acute complication of diabetes. While Celastrol has been reported to exert beneficial effects on obesity; its potential role in ketogenesis remains unclear. In this study, Celastrol administration significantly attenuates the fasting-induced elevation of blood {beta}-hydroxybutyrate. Moreover, a 7-day course of Celastrol (1 mg/kg/day) leads to reductions in body weight and fat mass. Mechanistically, Celastrol specifically downregulates HMGCS2 expression and suppressess hepatic ketogenesis through inhibiting PPAR expression in the short term ([≤] 2 days). However, after prolonged treatment for 7 days, Celastrol modulates both PPARand serum free fatty acids (FFAs) levels. Furthermore, anti-ketogenic effect of Celastrol is abolished in Ppar{square} /{square} mice. Importantly, Celastrol effectively ameliorates SGLT2i-induced hyperketonemia. In summary, Celastrol curbs hepatic ketone overproduction in a PPAR-dependent manner, indicating its protective potential against SGLT2i-induced hyperketonemia.

molecular biology↗

bioRxiv2026

HalluCodon enables species-specific codon optimization using multimodal language models

Codon optimization is widely used in transgenic crop development, plant synthetic biology, and molecular farming to improve heterologous protein expression in plant cells. Increasing availability of plant omics data now enables optimization strategies that account for species-specific sequence features. We developed HalluCodon, a customizable framework that uses multimodal language models to design coding sequences tailored to individual plant species. The framework allows users to fine tune pre-trained protein and RNA language models with their own datasets to build species-specific codon optimization models. The current implementation includes base models trained on coding sequences and proteomes from fifteen plant species. HalluCodon generates coding sequences through a hallucination-based design strategy guided by two predictive modules that evaluate coding sequence naturalness (CodonNAT) and expression potential (CodonEXP). Benchmark tests using representative proteins show that the generated sequences reproduce host-specific codon usage patterns and support high expression levels in plant systems.

bioinformatics↗

bioRxiv2026

Box H/ACA snoRNP regulates lipid storage through insulin signaling pathway in Drosophila melanogaster

Text abstractsLipid homeostasis is essential for organismal physiology, and its disruption contributes to metabolic disorders. Using an unbiased genetic modifier screen in Drosophila, we identified GAR1, a core component of the box H/ACA small nucleolar ribonucleoprotein complex, as a pivotal regulator of systemic lipid storage. We show that the H/ACA snoRNP complex is essential for maintaining lipid droplet morphology in adipose tissue and preventing ectopic fat accumulation. Moreover, null mutants of Gar1 or Dkc1 exhibit severe developmental defects, including reduced body size and larval lethality. RNA-seq analysis revealed that Gar1 dysfunction triggered widespread alternative splicing defects, specifically targeting key transcripts within the insulin signaling cascade, including chico, Pi3K92E, sgg, and Lip4. Furthermore, knockdown of Gar1 impaired insulin signaling, as evidenced by the reduced membrane localization of the tGPH fluorescence. Genetic epistasis further positions GAR1 upstream of the lin-28/foxo axis, as knocking down lin-28 or foxo fully rescues the lipometabolic defects in GAR1-deficient animals. These findings reveal a previously unrecognized link between the snoRNP machinery and metabolic process, establishing the box H/ACA complex as an important coordinator that integrates RNA processing with insulin-mediated nutrient sensing to ensure developmental and lipid homeostasis. Article summaryLipid metabolism is tightly controlled by multiple factors. To find new regulators, the authors performed a genetic screen and identified a small nucleolar protein GAR1 participate in fat storage and larval development. They demonstrated a critical role of box H/ACA snoRNP complex in modulating alternative splicing and balancing insulin cascade. Blocking two insulin-related genes reversed the lipid defects caused by Gar1 loss. These findings revealed the box H/ACA complex integrates RNA processing with insulin-mediated nutrient sensing to ensure developmental and lipid homeostasis, offering a perspective for understanding the metabolic regulation network.

genetics↗

bioRxiv2026

Complete genome-derived metabolic interactions reveal impact of gut ecology on human health

Metabolic interactions govern gut microbiome assembly, yet functional rules remain obscured by genomic incompleteness and fragmentation. Here, we leverage 1,150 complete genomes to construct genome-scale metabolic models, demonstrating that draft genomes introduce systemic artifacts missing critical transport functions. We observe that metabolic interactions are intrinsically driven by genomic traits and niche specialization rather than random association. We stratifies strains into four ecological groups, including active players, resource predators, utilizers, and contributors, each of which exhibits distinct metabolite exchange/competition signatures. This functional architecture is strongly coupled to secondary metabolism. Applying this framework to inflammatory bowel disease revealed distinct temporal dynamics of ecological groups across disease subtypes, where group-specific dysbiosis predicted clinical phenotypes better than whole community profiles. Furthermore, integrating metabolic and co-occurrence networks to identify keystone for classifiers as features significantly improved disease diagnosis. Our study provides novel insights into gut metabolic interaction landscape, bridging the gap between genomic potential and clinical utility for precision microbiome therapeutics.

microbiology↗

bioRxiv2026

ProAR: Probabilistic Autoregressive Modeling for Molecular Dynamics

Understanding the structural dynamics of biomolecules is crucial for uncovering biological functions. As molecular dynamics (MD) simulation data becomes more available, deep generative models have been developed to synthesize realistic MD trajectories. However, existing methods produce fixed-length trajectories by jointly denoising high-dimensional spatiotemporal representations, which conflicts with MDs frame-by-frame integration process and fails to capture time-dependent conformational diversity. Inspired by MDs sequential nature, we introduce a new probabilistic autoregressive (ProAR) framework for trajectory generation. ProAR uses a dual-network system that models each frame as a multivariate Gaussian distribution and employs an anti-drifting sampling strategy to reduce cumulative errors. This approach captures conformational uncertainty and time-coupled structural changes while allowing flexible generation of trajectories of arbitrary length. Experiments on ATLAS, a large-scale protein MD dataset, demonstrate that for long trajectory generation, our model achieves a 7.5% reduction in reconstruction RMSE and an average 25.8% improvement in conformation change accuracy compared to previous state-of-the-art methods. For conformation sampling task, it performs comparably to specialized time-independent models, providing a flexible and dependable alternative to standard MD simulations.

molecular biology↗

bioRxiv2026

Macrophage-derived extracellular vesicles promote T cell-dependent inflammatory pain resolution

Inflammatory pain resolution is increasingly recognized as an active, immune-regulated process, yet the adaptive immune mechanisms that govern this process remain poorly defined. We previously demonstrated that intrathecal administration of macrophage-derived small extracellular vesicles (sEVs) from unstimulated (sEV) or LPS-stimulated (sEV+) RAW 264.7 cells accelerate resolution of complete Freunds adjuvant (CFA)-induced inflammatory pain in male mice. However, the immunological mechanisms underlying this effect remain undefined. Given growing evidence that T cells regulate inflammatory pain resolution, we investigated whether macrophage-derived sEVs engage adaptive immune pathways to promote recovery. In vitro, both sEV and sEV+ enhanced T cell activation, with sEV+ exhibiting greater immunostimulatory capacity. Direct effects on T cells were modest; instead, sEV+ induced robust antigen-presenting cell (APC)-dependent T cell activation characterized by increased costimulatory molecule expression and enhanced Th1 polarization. Loss-of-function and rescue studies in Rag2-/- mice demonstrate that T cells are required for late-phase sEV+-mediated inflammatory pain resolution. In vivo, sEV+ elicited immunostimulatory responses in intrathecal-draining cervical and CFA-draining sacral/internal iliac lymph nodes. Together, these findings identify adaptive immune engagement as a critical mediator of sEV+-induced pain resolution and position macrophage-derived sEVs as a cell-free immunotherapeutic modality that harnesses endogenous T cell-dependent mechanisms of active inflammatory pain resolution. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/706465v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@e49aa4org.highwire.dtl.DTLVardef@648c9forg.highwire.dtl.DTLVardef@14c3cc6org.highwire.dtl.DTLVardef@2a17f0_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

The Herbicide Glyphosate Promotes Hypertension via Gut Microbiota-Mediated Mechanisms

Glyphosate, the active ingredient in herbicide Roundup, is the most widely used environmental contaminant that has been extensively studied for its potential carcinogenic effects. In the US alone, a staggering 81% of the US population [≥]6 years of age is exposed to glyphosate. Notably, this coincides with the alarming rise in the incidence of hypertension, the single largest risk factor for global mortality through cardiovascular diseases. Here we asked if there is a link between glyphosate exposure and hypertension, the premise being that glyphosate targets the shikimate pathway present in gut microbiota coupled with more recent knowledge that gut microbiota causally regulate blood pressure. We hypothesized that glyphosate elevates hypertension through microbiota-mediated mechanisms and document a highly concerning detrimental effect of glyphosate by demonstrating a causal link between oral glyphosate exposure and significant elevation in blood pressure. Gut microbiota was identified as the central mediator of this effect. Mechanistically, glyphosate-mediated elevation in blood pressure was through disruption of both gut-liver and gut-vascular homeostasis via FXR-signaling and accumulation of the microbial metabolite shikimic acid, respectively. Together, these findings underscore the need to reconsider the unabated use of this herbicide, which adversely affects a cardinal sign of health.

physiology↗

bioRxiv2026

Characterization of nanoparticles and fluorescent recombinant extracellular vesicles with three high-sensitivity flow cytometers

High-sensitivity flow cytometry (FC) allows multiparametric analysis of nanoparticles (NPs) and extracellular vesicles (EVs). With new instruments available, studies that evaluate their performance using the same materials in a controlled environment are required. Here, we performed a comparative study to investigate the capabilities of three flow cytometers, namely the NanoFCM (NF), BD Influx (IF) and CytoFLEX LX (CF). Firstly, we analyzed a mixed population of silica NPs (SiNPs, 68, 91, 114 and 155 nm) by using light-scatter based detection thresholds (SSC, FSC, VSSC) across a concentration range from 106 to 109 particles/mL. Next, we analyzed fluorescent recombinant EVs (rEVs) by comparing light-scatter based thresholding (488 nm SSC available for all platforms), the combination of SSC thresholding with a fluorescent gate, and fluorescent thresholding for their qualitative and quantitative analysis. We here provide the strengths and limitations for each platform regarding the analysis of differently sized NPs at different sample concentrations.

cell biology↗

bioRxiv2026

MolSpecFlow: Mass-Constrained Hybrid Flow Matching for Joint Molecular-Spectral Analysis

Identifying the "dark matter" of the chemical universe requires bridging the fundamental gap between molecules and mass spectra. Existing approaches struggle to accurately map between these distinct data formats, often yielding results that are either chemically implausible or inconsistent with the physical evidence. We introduce MolSpecFlow, a unified foundation model pretrained on 100 million molecules and 42 million spectra, which leverages a hybrid flow matching framework to orchestrate optimal transport paths for spectral peaks and discrete probability flows for molecular tokens. Furthermore, to guarantee the physicochemical validity of the generated structures, we incorporate explicit rule-based constraints into the generative process, utilizing a token-level mass control mechanism that strictly enforces alignment with the precursor molecular weight. MolSpecFlow establishes a new state-of-the-art on the MassSpecGym benchmark, surpassing diffusion and retrieval baselines in de novo generation (Top-1 accuracy +35%), spectral simulation, and molecular retrieval, demonstrating the power of physics-grounded unified modeling.

bioinformatics↗

bioRxiv2026

Microglial epigenetic memory is associated with accelerated resolution of inflammatory pain induced by prophylactic macrophage-derived small extracellular vesicles

Small extracellular vesicles (sEVs) including exosomes play an important role in intercellular communication and can exert immunomodulatory effects in recipient cells. We have shown that a single prophylactic intrathecal injection of sEVs from RAW 264.7 macrophages two weeks prior, promotes faster resolution of mechanical and thermal hypersensitivity in the complete Freunds adjuvant (CFA) mouse model of inflammatory pain. How this long-term memory develops, and how sEVs regulate immune responses are unknown. Recent studies have shown that priming microglia with inflammatory stimuli can enhance or suppress responses to a delayed secondary insult via epigenetic modifications. We hypothesized that prophylactic intrathecal administration of macrophage-derived sEVs confers accelerated resolution of inflammatory pain by reprogramming epigenetic memory in spinal microglia in recipient CFA model mice. To determine whether prophylactic sEVs could attenuate pain in the absence of microglia when administering sEVs, we ablated microglia using a colony-stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622. sEV-induced pain prophylaxis was completely abolished in PLX5622-fed mice, indicating that microglia are required to be present during sEV administration to confer early resolution of inflammatory pain hypersensitivity. ChIP-seq analysis in spinal microglia 14 days after sEV administration (prior to CFA) revealed an increased number of gene loci enriched for H3K4me1, a hallmark of innate immune memory. Furthermore, inhibiting the H3K4 mono-methyltransferase SETD7 abolished sEV-induced pain attenuation. Our findings indicate that both microglia and its epigenetic reprogramming contribute to pain prophylaxis induced by macrophage-derived sEVs, providing novel insights into the development of non-addictive preventive analgesia.

neuroscience↗

bioRxiv2026

Scalable Generation of Clinical-Grade Universal Human cDC1s Enables Potent Antitumor Immunotherapy

Despite decades of intensive clinical effort, monocyte-derived dendritic cell (DC) vaccines have not yet achieved sufficient clinical benefits in cancer therapy. Conventional type 1 DCs (cDC1s), a subset of antigen-presenting cells with superior cross-presentation capacity, are well established as pivotal mediators of antitumor immunity. However, their clinical translation has been hindered by the absence of scalable and efficient generation methods. Here, we develop a three-step strategy addressing this critical unmet need: a cost-effective, feeder cell-free, GMP-compatible approach enabling large-scale generation of cDC1s from human umbilical cord blood CD34+ hematopoietic stem and progenitor cells (CD34+ HSPCs). Starting from a single umbilical cord blood unit of CD34+ HSPCs, our method yields approximately 3.5x109 pure cDC1s--sufficient for over 700 therapeutic doses. These cDC1s exhibit robust antigen cross-presentation activity and substantial production of antitumor cytokines. Critically, in various humanized tumor mouse models, they elicit significantly stronger antitumor efficacy than either moDCs or PD-1 monoclonal antibody (mAb) alone, pronouncedly remodel the tumor microenvironment (TME), and synergize with PD-1 mAbs to achieve enhanced therapeutic effects. Furthermore, our system recapitulates the complete in vivo DC differentiation trajectory: from CD34+ HSPCs through early-pre-DCs and pre-DCs to mature subsets (cDC1s, cDC2s, DC3s, mregDCs, ASDCs). This platform thus provides a powerful tool to dissect the regulatory mechanisms governing human DC subset specification. Overall, this work overcomes a long-standing bottleneck in cDC1-directed cancer immunotherapy and accelerates the clinical translation of DC subset-selective immunotherapeutic strategies.

immunology↗