Biology subjects

Bao, Z.

Publications and source records attributed to Bao, Z..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Overcoming breeding constraints in polyploid oat from evolutionary insights

Polyploidy provides adaptive advantages in plants by buffering deleterious mutations1,2. While polyploidization can enhance agronomic traits such as increased biomass, known as the gigas effect1-4, increasing genetic gain in polyploid crops remains a critical but difficult goal due to the difficulty in dissecting complex trait inheritance5,6. Here we present chromosome-scale genome assemblies for 26 Avena taxa, spanning diploid, tetraploid, and hexaploid lineages. We traced four independent polyploidization events across the genus, including the formation of A. agadiriana as an allotetraploid (AgAgAg'Ag'), and revealed a reticulate evolutionary history shaped by gene flow involving four subgenomes (A, B, C, D), for example, the hybrid speciation of A. hirtula. Transcriptomic analysis of 286 samples across 11 tissues, combined with deleterious mutation analysis from a cultivated population of 112 accessions, showed that polyploidization led to widespread functional redundancy among homoeologs, supporting a genome-wide buffering effect. However, derived allele frequency analysis revealed that, while disrupting functional genes may yield desirable traits, the buffering effect impedes the fixation of beneficial loss-of-function mutations and thereby limits breeding efficiency. Based on these integrative analyses, we propose breeding strategies to circumvent these limitations by targeting beneficial loss-of-function alleles within the complex polyploid background of oat. Our study highlights broader challenges in the improvement of polyploid crops and provides a foundation for future breeding strategies.

evolutionary biology↗

bioRxiv2025

Biological characteristics of rabbit KLF12 and its regulation of proliferation and apoptosis of ovarian granulosa cells

Granulosa cells (GCs), as the largest somatic cell group in follicles, provide nutrients and microenvironment for oocyte growth and maturation. GC proliferation and apoptosis are influenced by several genes, with the Kruppel Like Factor 12 (KLF12) gene contributing to the modulation of several cellular activities. Nevertheless, the precise modulatory function of this gene within the context of ovarian GCs remains unelucidated. We cloned the KLF12 gene of New Zealand female rabbits, and evaluated its expression and localization in the ovaries of female rabbits of different ages by quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH). In order to determine the role of KLF12 in ovarian GCs, we used qRT-PCR, WB, CCK-8 and Annexin V-FITC/PI to detect the effect of KLF12 on GCs proliferation and apoptosis. The coding sequence of KLF12 gene of New Zealand female rabbit was predicted and cloned for the first time in this study. The coding region was 1209 bp, encoding 402 amino acids. KLF12 overexpression has a negative effect on the proliferation and cell cycle progression of rabbit GCs. KLF12 knockdown partially rescues GCs proliferation, accelerates GCs cycle progression, and promotes Estradiol (E2) and Progesterone (P) secretion. In addition, KLF12 was also proved to be a key regulator of PI3K/Akt signaling pathway in GCs. In conclusion, the study provides evidence that KLF12 plays a pivotal role in the maturation and proliferation of ovarian GCs in female rabbits. This work establishes a conceptual foundation for investigating deeper into the possible regulatory mechanisms underlying follicular development and growth. Author summaryGCs are essential for oocyte growth, not only providing necessary nutritional support for oocyte growth and maturation, but also constructing a key microenvironment. In this study, the biological function of KLF12 gene was systematically elucidated in rabbit for the first time. It was found that KLF12 inhibited follicular development by negatively regulating GCs proliferation and cell cycle. Combined with its effect on E2 and P secretion, the important regulatory role of KLF12 in follicular maturation and hormone balance was revealed. These innovative findings not only deepen the understanding of the regulatory network of ovarian development, but also provide a new theoretical basis for the basic research of reproductive biology. More importantly, it provides a potential molecular target for the development of new technologies to improve the reproductive efficiency of livestock. It also provides a valuable reference model for the study of the mechanism of human reproductive dysfunction related diseases.

genetics↗

bioRxiv2025

The structure of mitochondrial genomes is associated with geography in Arabidopsis thaliana

Chloroplasts and mitochondria are the primary sites for photosynthesis and respiration, each harboring its own unique genome. Although the organellar genomes are considerably smaller compared to the nuclear genome, they are nonetheless essential for survival of the organism. A common feature of many chloroplast and mitochondrial genomes is the presence of large repeated sequences longer than 1 kb. These can be either in inverted or direct orientation, and recombination between them leads to structural heteroplasmy. To understand the intraspecific evolution of organellar genomes, we assembled chloroplast and mitochondrial genomes of 143 A. thaliana accessions from PacBio HiFi sequencing data. We find large repeats to be associated with heteroplasmy and structural variation. Our extensive genome annotation identifies novel open reading frames (ORFs) in those accessions that lost large repeats, potentially introduced via horizontal gene transfer, illuminating additional paths for diversification of plant organelles. The loss of large repeats correlates with geography and phenotypes, pointing to their adaptive importance. The assembled and annotated organellar genomes constitute a rich source for future functional studies of the interaction between the three genomes of a plant.

evolutionary biology↗

bioRxiv2024

The 1001G+ project: A curated collection of Arabidopsis thaliana long-read genome assemblies to advance plant research

Arabidopsis thaliana was the first plant for which a high-quality genome sequence became available. The publication of the first reference genome sequence almost 25 years ago was already accompanied by genome-wide data on sequence polymorphisms in another accession, or naturally occurring strain. Since then, inventories of genome-wide diversity have been generated at increasingly precise levels. High-density genotype data for A. thaliana, including those from the 1001 Genomes Project, were key to demonstrating the enormous power of GWAS in inbred populations of wild plants, and the comparison of intraspecific polymorphism with interspecific divergence has illuminated many aspects of plant genome evolution. Over the past decade, an increasing number of nearly complete genome sequences have been published for many more accessions. Here, we highlight the diversity of a curated collection of previously published and so far unpublished genome sequences assembled using different types of long reads, including PacBio Continuous Long Reads (CLR), PacBio High Fidelity (HiFi) reads, and Oxford Nanopore Technologies (ONT) reads. This 1001 Genomes Plus (1001G+) resource is being made available at http://1001genomes.org. We invite colleagues with yet unpublished genome assemblies from A. thaliana accessions to contribute to this effort.

genomics↗

bioRxiv2024

LINC00599 Promotes Pulmonary Hypertension via LLPS with G3BP1 and MYH9

BACKGROUNDPulmonary hypertension (PH) represents a significant cardiovascular disorder marked by both functional and structural alterations within the pulmonary vasculature. Long non-coding RNAs (lncRNAs) have been closely associated with the pathogenesis and progression of PH. Nonetheless, the precise mechanisms by which lncRNAs interact with its downstream target molecules to modulate the disease remain inadequately elucidated. METHODSThe expression levels of LINC00599 were quantified in the lung tissues of mice and pulmonary arterial smooth muscle cells (PASMCs) under hypoxic conditions. The involvement of LINC00599 in the progression of PH and vascular remodeling was evaluated through in vivo studies. To investigate the mechanisms by which LINC00599 influences the proliferation of human PASMCs, small interfering RNA and overexpression plasmids were employed. RESUITSThe expression of LINC00599 is upregulated in the medial layer of pulmonary arteries in experimental models of PH and in hypoxic PASMCs. Administration of a single dose of lentivirus-mediated shRNA targeting LINC00599 effectively reverses hypoxic PH in murine models. LINC00599 plays a critical role in PASMC proliferation by modulating stress granule formation through N6-methyladenosine (m6A) modification and promoting proliferation via liquid-liquid phase separation with myosin heavy chain 9. Furthermore, the expression of LINC00599 is regulated by a super-enhancer, which is mediated by the transcription factor ZNF263. CONCLUSIONSThese findings demonstrate for the first time that LINC00599, involved in liquid-liquid phase separation, facilitates the progression of pulmonary hypertension by enhancing the proliferation of pulmonary artery smooth muscle cells. GRAPHIC ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/629439v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@7ac192org.highwire.dtl.DTLVardef@13a88b3org.highwire.dtl.DTLVardef@1e4c761org.highwire.dtl.DTLVardef@ddd105_HPS_FORMAT_FIGEXP M_FIG C_FIG What Is New?This study identified LINC00599 as a critical regulator of liquid-liquid phase separation through m6A modification and as a pivotal target in promoting the progression of PH. What Is Relevant?LncRNAs are intricately associated with the pathogenesis and progression of PH through the modulation of downstream target molecules. However, it remains unclear whether lncRNAs contribute to PH by forming specific subcellular structures with these target molecules. Furthermore, some studies have suggested that the increased presence of stress granules in PASMCs is implicated in the pathogenesis of pulmonary arterial hypertension. In this study, we provide evidence that LINC00599 promotes the development of PH by forming stress granules with its target proteins. Our findings indicate that the binding of LINC00599, modified with m6A, to G3BP1 and MYH9 in PASMCs suggests that the regulation of liquid-liquid phase separation by lncRNA m6A modification may represent a significant pathological mechanism underlying PH. What Are the Pathophysiological Implications?We found that LINC00599 levels were elevated in hypoxic PASMCs and experimental PH models. Knockout LINC00599 effectively prevented PH, indicating its potential as both a bomarker and therapeutic target for PH.

physiology↗

bioRxiv2024

GlioME: A Novel Organoid Model Retaining the Glioma Mi-croenvironment for Personalized Drug Screening and Thera-peutic Evaluation

Glioma is an aggressive brain tumor with a poor prognosis. Establishing an in vitro culture model that closely replicates the cellular composition and microenvironment of the original tumor has been challenging, limiting its clinical applications. Here, we present a novel approach to generate glioma organoids with a microenvironment (GlioME) from patient-derived glioma tissue. These organoids maintain the genetic and epigenetic characteristics of the primary tumor and preserve cell-to-cell interactions within the tumor microenvironment, including resident immune cells. Bulk RNA sequencing, whole exome sequencing, and DNA methylation analysis were used to confirm the molecular similarities between the organoids and primary glioma tissues. Immunofluorescence and flow cytometry were used to assess immune cell viability, comparing GlioME with floating glioma organoids. GlioME exhibited high responsiveness to chemotherapy and targeted therapy, demonstrating its potential for therapeutic screening applications. Notably, GlioME accurately predicted patient response to the recently approved MET inhibitor, vebreltinib. Thus, this organoid model provides a reliable in vitro platform for glioma microenvironment-related research and clinical drug screening.

cancer biology↗

bioRxiv2024

Gfa2bin enables graph-based GWAS by converting genome graphs to pan-genomic genotypes

Variation graphs offer superior representation of genomic diversity compared to traditional linear reference genomes, capturing complex features that are otherwise inaccessible to analysis. It seems self-evident that integrating these graphs with genome-wide association studies (GWAS) should enable more comprehensive understanding of genetic landscapes, potentially uncovering novel associations between genetic variations and traits. This approach takes full advantage of rich genomic information, thereby providing deeper insights into the genetic base of complex traits. Our tool, gfa2bin, offers multiple methods to (i) genotype variation graphs and (ii) convert the genotypes to well-established data formats for genome-wide association studies (GWAS). We demonstrate that variation graphs are feasible alternatives to traditional linear references for GWAS. Our case study using Arabidopsis thaliana and 1,695 traits shows that our approach complements SNP-based approaches, often identifying additional associations, with all associations having on average higher significance compared to SNP-based approaches. gfa2bin is implemented in Rust. Commented source code is available under MIT license at https://github.com/MoinSebi/gfa2bin. Examples of how to run gfa2bin are provided in the documentation. We added several Python scripts and a Snakemake pipeline for easy processing of our tool using larger data sets. In addition, we recommend using packing (https://github.com/MoinSebi/packing) for reduced storage and preprocessing (normalization) of sequence-to-graph alignments coverage.

bioinformatics↗

bioRxiv2024

Citalopram exhibits immune-dependent anti-tumor effects by modulating C5aR1+ TAMs and CD8+ T cells

Administration of selective serotonin reuptake inhibitors (SSRIs) is associated with a reduced cancer risk and shows significant anti-tumor effects across multiple tumor types, suggesting the potential for repurposing SSRIs in cancer therapy. Nonetheless, the specific molecular target and mechanism of action of SSRIs remain to be fully elucidated. Here, we reveal that citalopram exerts an immune-dependent anti-tumor effects in hepatocellular carcinoma (HCC). Interestingly, the anti-HCC effects of citalopram are not reliant on its conventional target, the serotonin transporter. Through various drug repurposing approaches, including global reverse gene expression profiling, drug affinity responsive target stability assay, and molecular docking, the complement component 5a receptor 1 (C5aR1) is identified as a new target of citalopram. C5aR1 is predominantly expressed by tumor-associated macrophages (TAMs), and citalopram treatment enhances local macrophage phagocytosis and elicits CD8+ T anti-tumor immunity. C5aR1 deficiency or depletion of CD8+ T cells hinders the anti-HCC effects of citalopram. Collectively, our study reveals the immunomodulatory roles of citalopram in inducing anti-tumor immunity, and provides a basis for considering the repurposing of SSRIs as promising anticancer agents for HCC treatment.

cancer biology↗

bioRxiv2024

Navigating the Cold: Integrative Transcriptome Sequencing Approach Reveals Ionoregulatory and Whole-Body Responses to Cold Acclimation in Drosophila ananassae

Understanding how species adapt to changing environments is a major goal in evolutionary biology and can elucidate the impact of climate change. Climate imposes inevitable effects on the geographical distribution of insects as their body temperature primarily depends on the environment. The vinegar fly Drosophila ananassae expanded from its tropical ancestral range to more temperate regions, which requires adaptation to colder temperatures. Transcriptome and genome-wide association studies focusing on the ancestral-range population identified the targets of selection related to ionoregulatory tissues. However, how cosmopolitan D. ananassae adapted to colder environments, where low temperatures last longer, is still unknown. Here, we present a study on the effect of long-term cold exposure on D. ananassae, examining the gene expression variation in the whole body and the ionoregulatory tissues, namely the hindgut and the Malpighian tubule. To elucidate molecular mechanisms of cold adaptation during species expansion, we included cold-tolerant and cold-sensitive strains from the ancestral species range and cold-tolerant strains from the derived species range. We show that cold acclimation improves cold tolerance and results in differential expression of more than half of the transcriptome in the ionoregulatory tissues and the whole body. Notably, we provide complementary insight into molecular processes at four levels: strains, populations, phenotypes, and tissues. By determining the biochemical pathways of phenotypic plasticity underlying cold tolerance, our results enhance our understanding of how environmental changes affect thermal adaptation in natural populations. SignificanceThe physiological mechanisms underlying cold tolerance of insects are complex. Our study integrates tissue-specific responses with whole-body response to cold and compares these responses in different populations, phenotypes, and strains of the vinegar fly Drosophila ananassae. The study reveals that the response to extended cold in the renal and intestinal tissues are different, that the tissue-specific responses can be masked in the whole body, and that the transcriptomic response to extended cold can depend on population of origin, cold tolerance phenotype, or strain. Overall, this study sheds light on insect cold adaptation in terms of transcriptomic response to cold acclimation in the ionoregulatory tissues and whole bodies.

evolutionary biology↗

bioRxiv2024

SSRI antidepressant citalopram reverses the Warburg effect to inhibit hepatocellular carcinoma by directly targeting GLUT1

Although there is growing appreciation for effective repurposing of selective serotonin reuptake inhibitors (SSRIs) for cancer therapy, particularly hepatocellular carcinoma (HCC), efforts are hampered by limited knowledge of their molecular targets and mechanism of action. Global inverse gene-expression profiling method, drug affinity responsive target stability assay, and in silico molecular docking analysis was performed to identify the targets of SSRIs. Murine subcutaneous, orthotopic models, and patient-derived xenograft were employed to explore the therapeutic effects and underlying mechanisms of SSRIs in HCC. The clinical relevance of SSRI use was verified with real world data. SSRIs exhibit significant anti-HCC effects independent of their known target serotonin reuptake transporter. The glucose transporter 1 (GLUT1) is identified as a new target of SSRIs. Citalopram binds to and antagonizes GLUT1, resulting in reduced glycolytic flux and ATP generation. Mutant GLUT1 in the binding site E380 of citalopram compromises the inhibitory effects of citalopram on the Warburg effect and tumor growth. In preclinical models, citalopram dampens the growth kinetics of GLUT1high liver tumors and displays a synergistic effect with anti-PD-1 therapy. Retrospective analysis of health records found that SSRIs use is associated with a lower risk of metastasis among HCC patients. Our study reveals an unprecedented role of SSRIs in cancer metabolism, and establishes a rationale for repurposing SSRIs as potential anticancer drugs for HCC.

cancer biology↗

bioRxiv2024

Gapless assembly of complete human and plant chromosomes using only nanopore sequencing

The combination of ultra-long Oxford Nanopore (ONT) sequencing reads with long, accurate PacBio HiFi reads has enabled the completion of a human genome and spurred similar efforts to complete the genomes of many other species. However, this approach for complete, "telomere-to-telomere" genome assembly relies on multiple sequencing platforms, limiting its accessibility. ONT "Duplex" sequencing reads, where both strands of the DNA are read to improve quality, promise high per-base accuracy. To evaluate this new data type, we generated ONT Duplex data for three widely-studied genomes: human HG002, Solanum lycopersicum Heinz 1706 (tomato), and Zea mays B73 (maize). For the diploid, heterozygous HG002 genome, we also used "Pore-C chromatin contact mapping to completely phase the haplotypes. We found the accuracy of Duplex data to be similar to HiFi sequencing, but with read lengths tens of kilobases longer, and the Pore-C data to be compatible with existing diploid assembly algorithms. This combination of read length and accuracy enables the construction of a high-quality initial assembly, which can then be further resolved using the ultra-long reads, and finally phased into chromosome-scale haplotypes with Pore-C. The resulting assemblies have a base accuracy exceeding 99.999% (Q50) and near-perfect continuity, with most chromosomes assembled as single contigs. We conclude that ONT sequencing is a viable alternative to HiFi sequencing for de novo genome assembly, and has the potential to provide a single-instrument solution for the reconstruction of complete genomes.

bioinformatics↗

bioRxiv2024

Gretl - Variation GRaph Evaluation TooLkit

Motivation: As genome graphs are powerful data structures for representing the genetic diversity within populations, they can help identify genomic variations that traditional linear references miss, but their complexity and size makes the analysis of genome graphs challenging. We sought to develop a genome graph analysis tool that helps these analyses to become more accessible by addressing the limitations of existing tools. Specifically, we improve scalability and user-friendliness, and we provide many new statistics for graph evaluation. Results: We developed an efficient, comprehensive, and integrated tool, gretl, to analyse genome graphs and gain insights into their structure and composition by providing a wide range of statistics. gretl can be utilised to evaluate different graphs, compare the output of graph construction pipelines with different parameters, as well as perform an in-depth analysis of individual graphs, including sample-specific analysis. With the assistance of gretl, novel patterns of genetic variation and potential regions of interest can be identified, for later, more detailed inspection. We demonstrate that gretl outperforms other tools in terms of speed, particularly for larger genome graphs. Availability and implementation: gretl is implemented in Rust. Commented source code is available under MIT licence at https://github.com/MoinSebi/gretl. Examples of how to run gretl are provided in the documentation. Several Jupyter notebooks are part of the repository and can help visualise gretl results.

bioinformatics↗

bioRxiv2024

Internalisation of integrin-bound extracellular matrix modulates invasive carcinoma cell migration

The interaction between cancer cells and the extracellular matrix (ECM) plays a pivotal role in tumour progression. While the extracellular degradation of ECM proteins has been well characterised, ECM endocytosis and its impact on cancer cell progression, migration and metastasis is poorly understood. ECM internalisation is increased in invasive breast cancer cells, suggesting it may support invasiveness. Here we developed a high-content screening assay to study ECM uptake. We identified that mitogen-activated protein kinase (MAPK) family members, MAP3K1 and MAPK11 (p38{beta}), and the protein phosphatase 2 (PP2) subunit PPP2R1A were required for the internalisation of ECM-bound 2{beta}1 integrin. Furthermore, 2{beta}1 integrin was necessary for macropinocytosis of soluble dextran, identifying it as a novel and targetable regulator of macropinocytosis in cancer. Moreover, disruption of 2 integrin, MAP3K1, MAPK11 and PP2R1A-mediated ECM internalisation significantly impaired cancer cell migration and invasion in 2D and 3D culture systems. Finally, 2{beta}1 integrin and MAP3K1 expression were significantly upregulated in pancreatic tumours and correlated with poor prognosis in pancreatic cancer patients. Strikingly, MAP3K1, MAPK11, PPP2R1A and 2 integrin expression were higher in chemotherapy-resistant tumours in breast cancer patients. Our results identified the 2{beta}1 integrin/p38 signalling axis as a novel regulator of ECM endocytosis, which drives invasive migration and tumour progression.

cancer biology↗

bioRxiv2023

Spiral NeuroString: High-Density Soft Bioelectronic Fibers for Multimodal Sensing and Stimulation

Bioelectronic fibers hold promise for both research and clinical applications due to their compactness, ease of implantation, and ability to incorporate various functionalities such as sensing and stimulation. However, existing devices suffer from bulkiness, rigidity, limited functionality, and low density of active components. These limitations stem from the difficulty to incorporate many components on one-dimensional (1D) fiber devices due to the incompatibility of conventional microfabrication methods (e.g., photolithography) with curved, thin and long fiber structures. Herein, we introduce a fabrication approach, "spiral transformation'', to convert two-dimensional (2D) films containing microfabricated devices into 1D soft fibers. This approach allows for the creation of high density multimodal soft bioelectronic fibers, termed Spiral NeuroString (S-NeuroString), while enabling precise control over the longitudinal, angular, and radial positioning and distribution of the functional components. We show the utility of S-NeuroString for motility mapping, serotonin sensing, and tissue stimulation within the dynamic and soft gastrointestinal (GI) system, as well as for single-unit recordings in the brain. The described bioelectronic fibers hold great promises for next-generation multifunctional implantable electronics.

bioengineering↗

bioRxiv2023

Topographical analysis of immune cell interactions reveals a biomechanical signature for immune cytolysis

Immune cells live intensely physical lifestyles characterized by structural plasticity, mechanosensitivity, and force exertion. Whether specific immune functions require stereotyped patterns of mechanical output, however, is largely unknown. To address this question, we used super-resolution traction force microscopy to compare cytotoxic T cell immune synapses with contacts formed by other T cell subsets and macrophages. T cell synapses were globally and locally protrusive, which was fundamentally different from the coupled pinching and pulling of macrophage phagocytosis. By spectrally decomposing the force exertion patterns of each cell type, we associated cytotoxicity with compressive strength, local protrusiveness, and the induction of complex, asymmetric interfacial topographies. These features were further validated as cytotoxic drivers by genetic disruption of cytoskeletal regulators, direct imaging of synaptic secretory events, and in silico analysis of interfacial distortion. We conclude that T cell-mediated killing and, by implication, other effector responses are supported by specialized patterns of efferent force.

immunology↗

bioRxiv2023

Structural RNA components supervise the sequential DNA cleavage in R2 retrotransposon

Retroelements are the widespread jumping elements considered as major drivers for genome evolution, which can also be repurposed as gene-editing tools. Here, we determined the cryo-EM structures of eukaryotic R2 retrotransposon with ribosomal DNA target and regulatory RNAs. Combined with biochemical and sequencing analysis, we revealed two essential DNA regions, Drr and Dcr, required for R2 recognition and cleavage. The association of 3 regulatory RNA with R2 protein accelerates the first-strand cleavage, blocks the second-strand cleavage, and initiates the reverse transcription starting from the polyA tail. Removing 3 regulatory RNA by reverse transcription allows the association of 5 regulatory RNA and initiates the second-strand cleavage. Our work explained the DNA recognition and supervised sequential retrotransposition mechanisms by R2 machinery, providing novel insights into the retrotransposon and application reprogramming.

molecular biology↗

bioRxiv2023

Building pangenome graphs

Pangenome graphs can represent all variation between multiple reference genomes, but current approaches to build them exclude complex sequences or are based upon a single reference. In response, we developed the PanGenome Graph Builder (PGGB), a pipeline for constructing pangenome graphs without bias or exclusion. PGGB uses all-to-all alignments to build a variation graph in which we can identify variation, measure conservation, detect recombination events, and infer phylogenetic relationships.

bioinformatics↗

bioRxiv2022

In situ genetically targeted chemical assembly of polymers on living neuronal membranes

Multicellular biological systems, most notably living neural networks, exhibit highly complex physical organization properties that pose challenges for building cell-specific and biocompatible interfaces. We developed a novel approach to genetically program cells to chemically assemble artificial structures that modify the electrical properties of neurons in situ, opening up the possibility of minimally-invasive cell-specific interfaces with neural circuits in living animals. However, the efficiency and biocompatibility of this approach were challenged by limited membrane targeting of the constructed material. Here, we report a method with significantly improved molecular construct properties, which expresses highly localized enzymes targeted to the plasma membrane of primary neurons with minimal intracellular retention. Polymers synthesized in situ by this approach form dense clusters on the targeted cell membrane, and neurons remain viable after polymerization. This platform can be readily extended to incorporate a broad range of materials onto the surface membranes of specific cells within complex tissues, using chemistry that may further enable the next generation of interfaces with living biological systems.

bioengineering↗