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Biology subjects

Du, C.

Publications and source records attributed to Du, C..

At least 19 recordsLinked to original sources

Plant-associated Streptomyces detoxify the mycotoxin fusaric acid by amino acid conjugation

Streptomycetes are prevalent members of soil and plant microbiomes, yet how they cope with toxins produced by root-infecting fungal pathogens remains poorly understood. Plant pathogenic Fusarium species produce the mycotoxin fusaric acid (FA) that contributes to virulence and perturbs rhizosphere microbiome dynamics. Here, we show that root-colonising Streptomyces sp. ATMOS43 neutralizes FA through amino acid conjugation. Metabolomics revealed the formation of single amino acid and dipeptidyl conjugates of FA, with FA-Ser as a major conjugate that lacked detectable toxicity in in vitro and in planta assays. Proteomics and physiological analyses revealed that FA toxicity involves, in part, zinc chelation, which is abolished upon conjugation of FA to Ser. Co-cultivation experiments further showed that Streptomyces sp. ATMOS43 restores growth of FA-sensitive streptomycetes, indicating that conjugation can mitigate the impact of FA on plant microbiome assembly. Together, our findings show that plant-associated streptomycetes can protect plants by directly inhibiting Fusarium growth and by neutralizing its toxic virulence factor FA.

microbiology↗

Ecologically inspired assembly of a Bacillales synthetic community for lignin degradation

Lignin remains a major bottleneck in biomass valorization due to its heterogeneous and recalcitrant structure. Traditionally, lignin degradation has been developed using a single-microorganism or single-enzyme approach, with efforts focused on identifying ligninolytic activities of individual bacteria or fungi. Here, we establish a framework for designing lignin-degrading synthetic microbial communities (SynComs) by integrating top-down ecological filtering with bottom-up trait-based selection. This approach enables the selection of bacteria with ligninolytic capacity while retaining community members that form strong biofilms and contribute indirectly to overall community function. Proteomic profiling uncovered lignin-driven functional reprogramming of the SynCom, highlighting strain-specific enzymatic specializations that collectively enable lignin depolymerization. Our work highlights the potential of SynComs for lignin degradation and shows how rationally designed, functionally partitioned communities can enhance lignin conversion.

microbiology↗

Characterizing Functional Clusters of V4 Neurons in Digital Twins

Neurons in primate visual cortical area V4 display tuning for multiple visual features, including color, shape, texture, and depth. Whether and how these neurons are organized into functional architectures remains largely unknown. Using two-photon calcium imaging in anesthetized macaques, we recorded responses of hundreds of V4 neurons to natural images and used these data to train deep convolutional neural network models (digital twins), obtaining synthetic images (SI) that maximized neuronal responses. Based on their SIs, these neurons clustered into classes that spatially matched the orientation, color, and curvature maps from intrinsic signal imaging. Furthermore, lesion study in digital twins revealed different integration rules for different neuron classes. Thus, digital twins of V4 neurons can be applied as a promising tool to characterize neurons fundamental features, which underlie the functional clustering in this area. HighlightsO_LINeurons in V4 are examined with two-photon calcium imaging and DCNN modeling (digital twins) C_LIO_LISynthetic images derived from neurons digital twins reveal distinct neuron groups C_LIO_LIThese groups match functional types defined by intrinsic signal optical imaging C_LIO_LILesion study in digital twins demonstrates neural mechanisms underlying feature tuning C_LI

neuroscience↗

A phosphorylation-dependent mechanism controls splice variant-specific S-palmitoylation of cardiac Kv4.3

S-palmitoylation modulates the activity of many cardiac ion channels, yet the upstream signals that control this post-translational modification (PTM) are poorly defined. Here we identify a phosphorylation-dependent mechanism that governs splice variant-specific S-palmitoylation of the potassium channel Kv4.3. Using Acyl-RAC in native tissue and heterologous cells, we map palmitoylation to C546/547 in the intrinsically disordered Kv4.3 C-terminal tail. The short Kv4.3 splice variant Kv4.3S is [~]2.5-3-fold more palmitoylated than the long splice variant Kv4.3L, and systematic mutagenesis localises the dominant inhibitory determinant of Kv4.3 S-palmitoylation to residues 488-498 within the Kv4.3L-specific splice insert. KChIP2.1 promotes accumulation of a post-translationally modified Kv4.3 species that is selectively S-palmitoylated, and nanobody-targeted dephosphorylation removes this species and reduces Kv4.3 S-palmitoylation. Phos-tag electrophoresis and C-terminal truncation mapping identify S538 as the principal phosphorylation site enabling Kv4.3 S-palmitoylation; mutation of S538 markedly reduces formation of the palmitoylation-competent species. TurboID proximity-labelling and biochemical assays indicate that phosphorylation enhances recruitment of Kv4.3 to zDHHC5. Acute kinase inhibition rapidly eliminates phosphorylation but only gradually reduces palmitoylation, revealing temporal uncoupling between these PTMs. Functionally, non-palmitoylatable Kv4.3S exhibits larger peak currents, faster inactivation, and a left-shifted activation curve, consistent with palmitoylation limiting channel function and modulating gating transitions. Together, these findings identify phosphorylation of S538 as a priming modification that licenses Kv4.3 S-palmitoylation at C546/547, explain splice-variant differences in S-palmitoylation, and define a PTM cascade that tunes Kv4.3 channel behaviour.

cell biology↗

A global regulatory atlas of Streptomyces reveals conserved and diversified transcriptional networks across actinomycetes

Transcriptional regulatory networks determine how bacteria integrate environmental signals with growth, metabolism and stress adaptation. Actinomycetes encode exceptionally large repertoires of transcription factors (TFs) coordinating morphological development, environmental adaptation and specialized metabolism, yet their regulatory networks remain poorly defined. Here, we apply DNA affinity purification sequencing (DAP-seq) to 789 predicted TFs of Streptomyces coelicolor, generating genome-wide binding maps for 393 regulators and expanding the experimentally supported regulome from [~]8% to [~]50%. Integration with ChIP-seq reveals pleiotropic regulators and hierarchical network architecture linking primary metabolism, development and biosynthetic gene clusters (BGCs). Multiplexed DAP-seq (multiDAP) across 16 additional actinomycetes uncovered deeply conserved regulatory circuits alongside widespread divergence in TF-target interactions. Together, these data establish a regulatory atlas for Streptomyces and related actinomycetes, enabling researchers to explore control of genes, pathways, BGCs and conserved network modules. This provides a foundation for predictive analysis and engineering of complex bacterial phenotypes in biotechnology and medicine.

microbiology↗

NAADP elicits two-pore channel currents by lifting Lsm12-mediated inhibition of PI(3,5)P2 activation

Mammalian two-pore channels (TPCs) are endolysosomal cation channels that regulate membrane trafficking and ionic homeostasis and have been strongly implicated in nicotinic acid adenine dinucleotide phosphate (NAADP) signaling. We previously identified Lsm12 as an NAADP receptor and TPC-interacting protein required for NAADP-evoked Ca2+ mobilization from acidic organelles; however, how NAADP-Lsm12 coupling regulates TPC gating has remained unclear. Here, we show that Lsm12 acts as a potent antagonist of phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2]-dependent TPC activation. Purified Lsm12 strongly inhibited PI(3,5)P2-evoked currents of TPC1 and TPC2, and endogenous Lsm12 similarly suppressed TPC2 activity in cells. Mechanistically, Lsm12 reduces the apparent sensitivity of TPC2 to PI(3,5)P2 through a competitive mechanism that depends on the concentrations of both Lsm12 and PI(3,5)P2, as well as on Lsm12-TPC interaction. Importantly, NAADP specifically and dose-dependently reverses Lsm12-mediated inhibition, restoring TPC currents only in the presence of PI(3,5)P2 or an intact PI(3,5)P2-binding site on TPCs. Consistently, acute sequestration of endogenous PI(3,5)P2 reduces NAADP-evoked cytosolic Ca2+ signals. These findings support a model in which Lsm12 tonically restrains PI(3,5)P2-dependent TPC gating, whereas NAADP binding to Lsm12 relieves this inhibition to permit channel activation. Our study therefore establishes a mechanistic link between NAADP signaling and phosphoinositide-dependent TPC gating and provides a working model for understanding NAADP-evoked Ca2+ release from acidic stores.

cell biology↗

Stage-adaptive integration of polydopamine promotes hPSC-derived alveolar organoids differentiation and maturation

Human pluripotent stem cell (hPSC)-derived alveolar organoids (ALOs) have emerged as a powerful tool for modeling human lung development and disease, and accelerating respiratory drug discovery. However, achieving the functional maturation of ALOs remains challenging. Polydopamine (PDA) is a mussel-inspired polyphenolic biomaterial with antioxidant and adhesive properties that can be deployed as surface coatings and nanoparticles (NPs) in cell culture systems. Here, we integrate PDA coatings and NPs sequentially in a stage-adaptive manner throughout the hPSC-derived ALOs differentiation system and study their contributions to ALOs maturation. Our results demonstrated PDA coating yielded more anterior foregut endoderm (AFE) spheroids by strengthening the interaction between Matrigel and substrate. Bulk RNA-seq revealed enrichment of cell-cell and cell-extracellular matrix interactions by PDA. The subsequent incorporation of PDA NPs in Matrigel at lung progenitor cells (LPCs) stage significantly mitigated reactive oxygen species (ROS) accumulation and enhanced LPCs generation. Functionally, AT2 cells in ALOs exhibit characteristic lysosome-to-lamellar body (LB) maturation due to the traffic of internalized PDA NPs to endolysosome. Transcriptomics further indicated enrichment of endocytic-phagosome and epithelium development pathways by PDA treatment. Together, our study establishes a stage-adaptive-integrated PDA strategy throughout hPSC-to-ALOs differentiation and demonstrates that PDA robustly enhances ALOs maturation and secretory function. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=178 SRC="FIGDIR/small/708928v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@88208dorg.highwire.dtl.DTLVardef@1111590org.highwire.dtl.DTLVardef@9ea9b0org.highwire.dtl.DTLVardef@969fad_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Geometric structure of features underlies human VTC object recognition.

The ventral temporal cortex (VTC) plays a crucial role in human object recognition. Within VTC neural space, object-specific domains align with domain-general features, e.g. face- and scene-domain align with the feature distribution of animacy, generating a hierarchical knowledge structure for categorization. However, the neural process of integrating information from VTC to distinguish different objects remains unclear. Here, we employed a combination of ANN modeling, functional MRI, and MEG to investigate how VTC features affect object manifold separability. The representational geometry analysis shows that domain-general features in VTC form a unique structure, different from ANN, to assist object classification. Moreover, VTC dynamically adjusts the geometrical relationship of these features during object recognition, influencing the geometrical properties of object manifolds and, consequently, their separability. These findings advance our understanding of the neural computation involved in VTC object recognition, revealing how downstream neurons can flexibly access category information in diverse recognition tasks.

neuroscience↗

Sensorimotor dynamics differentiate singing and speaking

Singing and speaking often dissociate clinically--people who stutter can sing fluently, and individuals with aphasia and speech output problems from stroke may express sentences fluently in song--yet the neural mechanisms of this centuries-old clinical phenomenon remain unclear. We recorded intracranial EEG while neurosurgical patients produced matched sentences by singing or speaking, sampling millimeter- and millisecond-scale activity across both hemispheres. During articulation, high-frequency activity (70-150 Hz) lateralized oppositely across behaviors, with right-dominant sensorimotor cortex (SMC) activation for singing and left-dominant activation for speaking. Phase-amplitude coupling revealed that mu-band ([~]10 Hz) phase locally organized HFA in left SMC in a channel-specific, spatially interdigitated architecture preserved across both behaviors. Mu-band synchrony in speaking showed an early left-led pattern, whereas singing exhibited a ramping of synchrony within the left sensorimotor cortex and between the two motor cortices, supporting progressive interhemispheric recruitment. Frequency-domain Granger- Geweke causality revealed that the left primary somatosensory cortex drives both motor cortices at speech onset. In contrast in singing, control over motor cortices relied on both hemispheres. Singing and speaking engage a shared mu-coupled sensorimotor substrate through distinct recruitment dynamics.

neuroscience↗

Representation, Alignment, and Generation: A Comprehensive Survey of Foundation Models for Non-Invasive Brain Decoding

The ability to decode human thoughts, intentions, and perceptions directly from non-invasive brain recordings holds transformative potential for healthcare, communication, and human-computer interaction. However, translating the safety and scalability of methods like Functional Magnetic Resonance Imaging (fMRI), Electroencephalography (EEG), and Magnetoencephalography (MEG) into real-world utility has traditionally been hindered by low signal-to-noise ratios, limited spatial-temporal resolution, and the difficulty to collect large-scale high-quality data from an individual user. Recently, the emergence of Foundation Models (FMs)--large-scale, pre-trained architectures--has expanded the feasible operating region of non-invasive brain decoding under controlled protocols, primarily through representation learning, neuro-semantic alignment, and strong generative priors. However, evidence for robust cross-subject and real-world deployment remains uneven, as many results are still demonstrated on limited cohorts or highly controlled settings. This survey provides a comprehensive overview of how FMs are redefining the boundaries of non-invasive brain decoding. We propose a unified methodological framework that synthesizes recent advancements into a coherent process: extracting robust, transferable representations from noisy neural signals; aligning these signals with the rich semantic spaces of pre-trained vision and language models; and leveraging powerful conditional generative priors to reconstruct high-fidelity outputs. We systematically review state-of-the-art applications across three key domains: visual reconstruction, language and speech decoding, and auditory processing. Furthermore, we critically examine the persisting challenges of computational efficiency, cross-subject generalization, and privacy governance. By mapping the current landscape and identifying key gaps, this work outlines a strategic research agenda aimed at transitioning FM-driven neurotechnology from laboratory proofs-of-concept to reliable, real-world applications.

neuroscience↗

Cold Atmospheric Plasma for Alzheimer's disease

Lightning has been proposed as a pivotal energy source driving prebiotic chemical evolution and early life processes. Similarly, external physical stimuli such as sound and light have been shown to modulate neurophysiological activity and mitigate Alzheimers disease (AD) pathology by promoting amyloid-{beta} (A{beta}) clearance. Here, we demonstrate that cold atmospheric plasma (CAP) acts as a joule-level analog of lightning, integrating light, sound, and reactive species to modulate AD progression in a mouse model. Using multimodal analyses, we show that CAP treatment enhances key neuroimmune signaling pathways in an AD murine model, including microglial activation, without inducing pathological alterations at the functional, transcriptomic, or proteomic levels in healthy mice. These findings highlight CAP as a safe and efficacious modality for modulating neurodegenerative processes, establishing a foundation for its therapeutic translation in AD and related disorders.

bioengineering↗

Paenitracins, a novel family of bacitracin-type nonribosomal peptide antibiotics produced by plant-associated Paenibacillus species

The growing threat of antimicrobial resistance necessitates the discovery of novel antibiotics with activity against drug-resistant pathogens. Members of the genus Paenibacillus are a rich source of nonribosomal peptides (NRPs), including well-known antibiotics such as polymyxins, paenibacterin and tridecaptins. Here we use a targeted Mass-QL-based mass spectrometry approach to identify the NRPs produced by a collection of 227 taxonomically diverse plant-associated Paenibacillus strains, providing detailed insights into their NRP-producing potential. Using MassQL to zoom in specifically on NRPs containing basic amino acids, we discovered a novel family of bacitracins, which we designated paenitracins. The paenitracins are the first bacitracin-type peptides reported in Paenibacillus, and are distinguished from canonical bacitracins by three previously unseen amino acid substitutions. The paenitracins exhibit potent activity against Gram-positive pathogens, including vancomycin-resistant Enterococcus faecium E155. Our work provides a novel metabolomics- and genomics-guided workflow for the discovery of bioactive NRPs as a strategy to prioritize natural product chemical space and accelerate antibiotic discovery. IMPORTANCEMembers of the genus Paenibacillus play an important role in soil ecology, producing a range of important nonribosomal peptides (NRPs) that protect their eukaryotic host. A collection of plant-associated Paenibacillus spp. was analyzed for their phylogenetic and metabolic diversity. We developed a novel discovery pipeline that combines feature-based molecular networking with MassQL queries to systematically prioritize bioactive NRPs containing basic amino acids. Thus we provide a comprehensive genus-wide inventory of NRPs produced by Paenibacillus spp. We thereby identified the paenitracins, a new subfamily of bacitracins active against multidrug-resistant Gram-positive pathogens. Our pipeline enables the discovery of novel peptidic natural products to accelerate the prioritization of chemical space for antibiotics.

microbiology↗

Pheromone circuits and transcriptional cascades modulating transcriptional and chromatin states in the Drosophila central brain with social experience

Social experience significantly influences the behavioral and physiological responses of animals, including humans. In many animals, social isolation increases aggression, courtship, locomotion, and feeding while disrupting sleep. This occurs when peripheral neurons detect social signals, such as pheromones, which activate decision-making circuits in the brain. However, the molecular and circuit mechanisms of how chronic social isolation or enrichment alter gene expression and affect neuronal function and behavior remain unclear. In this study, we examined how transcription patterns and chromatin marks in male Drosophila brains change in response to social experience, and the effect of pheromone circuits and transcription factors involved in social circuit function. We focused on pheromone receptors Or47b and Or67d, as well as transcription factors FruM and DsxM. Our findings suggest that social experience affects multiple genes in the central brain. Disrupting Or47b, Or67d, FruM, and DsxM function moderated the transcriptional responses through antagonistic interactions. Specifically, Or47b circuits predominantly mediated transcriptional responses to social isolation through DsxM function, while Or67d and FruM regulated responses to group housing. Notably, mutants of fruM and dsxM exhibited more extensive transcriptional changes in the brain than Or mutants, especially for FruM/DsxM target genes. While social experience did not lead to detectable alterations in the overall chromatin profile in the whole brain, mutants of the four genes resulted in significant changes in the enrichment of H3K4me3 and RNA polymerase II (RNAPolII) compared to wild type. Furthermore, mutants in fruM and dsxM generally eliminated social experience-dependent changes in sleep and locomotion behaviors, whereas Or mutants exhibited more modest disruptions. Overall, our results uncover the pheromone circuits and transcriptional cascades in regulating molecular and behavioral responses to social experience.

neuroscience↗

Morphological plasticity of endophytic Chitinophaga pinensis

Environmental changes, whether due to climate change or human influences, compromise the resilience of plants to biotic and abiotic stresses, such as pathogens, drought and heat. Plant microbiota are known to promote plant resilience. To be able to harness the power of the plant microbiome we need to identify microbiota with health-promoting properties. Recent studies have demonstrated that the bacterium Chitinophaga pinensis enhances plant health and increases resistance to fungal infections. Here, we show that C. pinensis exhibits an unusually high morphological plasticity, switching between a filamentous and a spherical cell state, each of which is characterized by a distinct transcriptional profile. Despite these transcriptional differences, spherical cells remained metabolically active and replicating, while lacking structural characteristics typically associated with dormant states. Furthermore, the spherical cell morphology of C. pinensis facilitates hitchhiking behaviour and motility via surfactin cheating, potentially influencing its dispersal and interactions within the plant microbiome. To investigate the structural dynamics and transcriptional adaptation of this plant endophyte, we applied a combination of microscopy and culture-based techniques. Taken together, our study provides new insights into the morphological flexibility and transcriptional regulation of the plant-beneficial C. pinensis.

microbiology↗

Social experience alters behaviors by reprogramming the Fruitless pathway and circadian state in Drosophila

From flies to humans, social experience affects various cognitive and behavioral processes. Previous studies have shown that group housing suppresses many behaviors like courtship, aggression, and feeding in Drosophila melanogaster, in addition to resetting the circadian state. Here, we focus on group housing-induced courtship suppression. To determine the mechanisms by which social experience modulates courtship behaviors, we performed bulk tissue RNAseq and single-cell RNAseq from cells expressing FruitlessM (FruM) and DoublesexM (DsxM), two transcription factors that label interconnected neural circuits for socially driven behaviors, from grouped or isolated male brains. These revealed that social isolation alters fru and dsx levels throughout the brain. Knocking down fruM in different fruM-positive neuron subpopulations in the brains has diverse effects on social experience-dependent changes in courtship. Furthermore, group housing increases the expression of stripe (sr) and Hormone receptor-like in 38 (Hr38) genes encoding neural activity-induced transcription factors in most neurons within social circuits. We found that knocking down sr in fruM-positive neurons effectively eliminates the impact of social experience by increasing courtship in group-housed males. Importantly, social experience also alters the expression of FruM/DsxM putative target genes regulating circadian states throughout the brain. Disrupting the function of multiple circadian genes diminishes the effect of group housing on courtship. Our findings suggest that group housing/social enrichment suppresses courtship by reprogramming the circadian arousal state, whereas courtship-elevating effects of social experience rely on unique influences of FruM expression and function in different neurons within social and clock circuits. These results are significant as they point to modulation of circadian arousal state as a possible central strategy for mediating the pleiotropic effects of social experience on organismal responses.

neuroscience↗

Serpine1 plays a critical role in Th17 cell differentiation and psoriasis pathogenesis

A large body of evidence indicates that Th17 cells play essential roles in mucosal immune responses and trigger autoimmune diseases, including multiple sclerosis, inflammatory bowel disease, and psoriasis. Targeting Th17 cells holds promise for therapeutic innovation. However, the molecular mechanisms underlying Th17 cell differentiation remain poorly understood. Here, we found that Serpine1 was preferentially induced in Th17 cells. Genetic ablation of Serpine1 inhibited Th17 cell polarization in vitro, reproducing the phenotype caused by pharmaceutical inhibition against Serpine1 product PAI-1. Moreover, we confirmed that, despite normal T-cell initiation in vivo, deletion or inhibition of Serpine1 significantly attenuated disease severity and notably reduced skin inflammation in an IMQ-induced psoriasis model. Notably, this protective effect was also recapitulated in the CD4 conditional knockout mouse pathogenic model, ruling out the non-T cell autologous effect of Serpine1. Collectively, our results revealed a critical role of Serpine1 in regulating Th17 cell differentiation and autoimmune diseases, suggesting that Serpine1 is a promising therapeutic target for autoimmune disease treatment. SignificanceUsing multiple genetic and pharmaceutical ablation model systems, we have demonstrated that Serpine1 plays a critical role in regulating Th17 differentiation and psoriasis pathogenesis. Serpine1 intervention attenuates disease symptoms in a psoriatic mouse model in a Th17 cell-dependent manner. This finding extends our understanding of Serpine1s role in inflammatory diseases, highlighting its therapeutic potential.

immunology↗

Antifungal biosynthesis by root-associated Streptomyces and Pseudomonas is elicited upon plant colonization

Plants are colonized by a diverse microbiome, with microorganisms residing inside and outside of plant tissues. Plants can harness the protective traits of their microbial inhabitants to ward off insect pests and fungal pathogens. However, current understanding of the role of commensal interactions on activating the desired microbial genomic traits remains limited. Here we show that biosynthesis of the antifungal 2,5-dihydro-L-phenylalanine (DHP) by the endophytic Streptomyces sp. PG2 is strongly induced upon colonization of Arabidopsis thaliana. DHP production protects the plant from infection by the fungal root pathogen Rhizoctonia solani, both in vitro and in vivo.. We identified the DHP biosynthetic gene cluster (BGC) and showed that heterologous expression of the BGC in the DHP non-producer Streptomyces coelicolor also conferred plant-inducible DHP production. The BGC was also found in plant-associated Gram-negative bacteria, and in Pseudomonas syringae FF5 we again observed strongly enhanced DHP production upon plant colonization. An ecology-inspired elicitor screen showed that L-valine and brassinosteroid hormones elicit DHP biosynthesis in the plant-beneficial Streptomyces sp. PG2, while L-valine also elicited DHP biosynthesis in S. coelicolor. In vivo experiments confirmed the stimulation of antifungal activity in Streptomyces sp. PG2 by L-valine, while brassinolide mutant plants showed reduced DHP induction. Conversely, neither L-valine nor brassinolide elicited the expression of the DHP BGC in the pathogenic P. syringae, revealing important divergence in the responses to plant signaling, which may reflect selectivity in how endosymbionts and pathogens respond to host cues. Collectively, our data demonstrate that plant colonization can elicit the biosynthetic potential of root-associated microbes, thereby enhancing plant resilience.

microbiology↗

Unraveling transposable element-mediated regulatory landscape in diverse human immune cells

Transposable elements (TEs) are key contributors to genetic novelty. Despite increasing evidence of their importance, their roles in shaping the regulatory landscape of diverse immune cell populations remain largely unclear. Using single-cell multiome data from human peripheral blood mononuclear cells, we annotated the cell-specific cis-regulatory elements for major immune cell populations and identified a highly cell-specific signature of the overrepresented TE families. Focusing on monocytes that bear fast-evolving transcriptomes, we found that high proportions of their enhancers are TE-derived and bound by multiple pioneer transcription factors. Among them, we confirmed that the core myeloid regulator SPI1 can bind and regulate hundreds of TE-derived enhancers, which further affect the expression of adjacent immune genes. Additionally, interspecies comparison reveals that non-conserved monocyte enhancers are frequently generated by lineage-specific TE insertions, and correlate with the evolved gene expression between human and mouse. Overall, our study supports the importance of TEs in shaping the regulatory landscape of diverse immune cell populations.

genomics↗