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Biology subjects

Zhong, T.

Publications and source records attributed to Zhong, T..

18 recordsLinked to original sources

Force-induced unfolding versus unbinding of a cellulosomal carbohydrate-binding module from cellulose interface

Carbohydrate-binding modules (CBMs) anchor microbial cellulosomes to cellulose surfaces, aiding biomass degradation under mechanical stress. To understand how mechanical pulling affects this process, we combine steered molecular dynamics (SMD) simulations with acoustic force spectroscopy (AFS) to investigate Clostridium thermocellum CBM3a unbinding from cellulose under different pulling configurations (C- versus N-terminus). Our SMD simulations reveal that C-terminal pulling induces substantial CBM3a unfolding prior to unbinding, whereas N-terminal pulling results in detachment with the protein largely intact. Unbinding proceeds via two distinct mechanisms across the planar binding motif: a TRP mode (initiating via TRP135) and a TYR mode (initiating via TYR84). AFS experiments corroborate the SMD findings, showing that C-terminal pulling yields lower rupture forces and a 7.5-fold higher unbinding off-rate compared to N-terminal pulling of CBM3a from cellulose. These results demonstrate that structural asymmetry and pulling orientation critically govern the mechanical stability, unfolding pathways, and cellulose-binding dynamics of cellulosomal proteins.

biophysics↗

An Expanded Lpt Pathway Couples Surface Lipoprotein Export to Outer Membrane Vesicle Biogenesis in Bacteroides

The ecological dominance of Bacteroidota in the human gut microbiota derives from their exceptional capacity to metabolize diverse dietary and host-derived glycans. This ability relies on surface-exposed lipoproteins (SLPs), which are displayed on the bacterial surface and selectively packaged into outer membrane vesicles (OMVs). Although SLP export and OMV biogenesis are tightly coupled, the mechanism linking these processes has remained unknown. Here, we identify LptZ, a previously uncharacterized protein, as a critical link between SLP surface translocation and OMV biogenesis. Cryo-electron tomography of the lptZ mutant revealed chains of vesicles tethered to the outer membrane, offering a rare glimpse into an arrested stage of OMV formation in which vesicle fission is impaired. Proteomic analysis further showed that, in the absence of LptZ, a subset of SLPs fails to reach the cell surface and instead accumulates at the inner membrane. Unexpectedly, LptZ associates with the lipopolysaccharide transport (Lpt) machinery and repurposes it for SLP translocation. Crosslinking experiments revealed selective associations between multiple SLPs and Lpt proteins, providing mechanistic evidence for the direct involvement of the Lpt machinery in SLP trafficking. We further show that the Bacteroides Lpt machinery contains previously unrecognized components, revealing an unanticipated level of specialization relative to canonical Lpt systems. Together, our findings uncover a previously unknown protein export pathway, expand the functional role of the Lpt machinery, and establish a direct mechanistic link between SLP translocation and OMV biogenesis in Bacteroidota.

microbiology↗

Bacterial nanotubes extend from a tubeosome organelle to establish an intercellular bridge

Bacterial nanotubes are widespread intercellular membranous bridges mediating molecular exchange among neighboring cells, yet their formation and dynamics remain largely unexplored. By combining live-cell imaging with in situ cryo-electron tomography, we describe nanotube biogenesis in the Gram-positive Bacillus subtilis. Nanotubes form elaborate, highly dynamic networks, with extending nanotubes exhibiting multidirectional movement toward nearby cells, repeatedly scanning their surface. Ultimately, nanotubes penetrate through the recipient cell wall to establish an intercellular bridge. Strikingly, nanotubes emerge within milliseconds from lipid-enriched sites representing a previously unrecognized membranous organelle, termed tubeosome, located in an unusual pseudo-periplasmic space beneath the cell wall. We present evidence that tubeosomes comprise proto-nanotube reservoirs that unfold to project nanotubes. Our study uncovers the tubeosome as a novel bacterial organelle and provides the first real-time visualization of intercellular bridge formation. As connecting nanotubes are found across bacteria, archaea, and eukaryotes, this mechanism may reflect a broadly conserved strategy for cellular communication.

microbiology↗

PRDM1 Drives Chemoradiotherapy-associated Enrichment of Adaptive NK Cells in Cervical Cancer

Chemoradiotherapy (CRT) induces not only direct tumor cell death but also extensive remodeling of the tumor immune microenvironment. Adaptive natural killer (aNK) cells, initially characterized in chronic viral infection, are increasingly recognized as functionally relevant immune populations in solid tumors, where they may contribute to antitumor immunity and immune memory. However, how aNK cells dynamically respond to chemoradiotherapy and the regulatory mechanisms underlying their activation in solid tumors remain poorly defined. To address this, we analyzed single-cell RNA sequencing data from cervical cancer patients collected before CRT, after the first CRT fraction, and after the second fraction. Single-cell profiling revealed a significant enrichment of aNK cells following CRT. Differential gene expression and pathway enrichment analyses demonstrated that CRT-associated aNK cells exhibit enhanced virus-defending programs with increased cytotoxicity. Among the differentially expressed genes, the transcription factor PRDM1 was consistently and robustly upregulated in aNK cells after both the first and second rounds of CRT. To investigate the functional role of PRDM1, we applied in silico perturbation analyses using scTenifoldKnk and CellOracle. Virtual knockout of PRDM1 resulted in a marked attenuation of effector programs and disruption of metabolic networks in aNK cells. Moreover, PRDM1 perturbation altered inferred cellular trajectories, reversing the progression toward the aNK cell state, suggesting a requirement for PRDM1 in maintaining aNK identity and functional maturation within the CRT-conditioned tumor microenvironment. Together, these findings identify PRDM1 as a key regulatory factor associated with the enrichment, functional activation, and trajectory stabilization of aNK cells following CRT in cervical cancer, providing insight into innate immune remodeling during CRT and highlighting PRDM1 as a potential target for enhancing radiotherapy-induced antitumor immunity.

immunology↗

Polyketide Synthase-Like Functionality Acquired by Plant Fatty Acid Elongase

Fatty acid elongation (FAE) typically proceeds through a four-step cycle of condensation, reduction, dehydration, and reduction to yield very long-chain fatty acids. Here, we describe a variation of this pathway in Orychophragmus limprichtianus, whose seed oil was found to contains previously unknown C24-C28 keto-hydroxy fatty acids that account for [~]25% of total fatty acids. Our studies revealed that these compounds are produced through an endoplasmic reticulum-localized discontinuous elongation process in which a 3-keto hydroxy intermediate bypasses full reduction and is extended through a polyketide synthase-like mechanism. Transcriptomic and functional assays identified two divergent enzymes, OlFAE1-2 and the low-activity ketoreductase OlKCR1-1, as central to this process. Protein modeling and mutant analysis suggest that specific amino acid substitutions underlie the altered activity of OlKCR1-1, enabling accumulation of keto intermediates. A portion of these unusual fatty acids accumulated in estolides, complex triacylglycerols that expand the chemical repertoire of seed oils. Together, our findings reveal unexpected flexibility in plant fatty acid elongation and provide new tools for engineering plants and microbes to produce renewable oils with tailored industrial functions.

plant biology↗

Dual Membrane-spanning Anti-Sigma 2 Controls OMV biogenesis and Colonization Fitness in Bacteroides thetaiotaomicron

Bacteroides spp. are Gram-negative, gut commensals that shape the enteric landscape by producing outer membrane vesicles (OMVs) that degrade dietary fibers and traffic immunomodulatory biomolecules. Understanding the mechanism behind OMV biogenesis in Bacteroides spp. is necessary to determine their role in the gut. Recent studies showed that mutation of Dual Membrane-spanning Anti-sigma factor 1 increased OMV production in Bacteroides thetaiotaomicron (Bt) by regulating members of its downstream regulon. Additional members of the Dma family have been identified, but very little is known regarding their roles in Bt. Here, we investigate the role of Dual Membrane-spanning Anti-sigma factor 2 (Dma2) in controlling OMV biogenesis in Bt. We employ biochemical and proteomic analyses to show that mutation of dma2 increases OMV production in a manner that is dependent on the expression of its cognate sigma factor, das2. The precise mechanism by which dma2 increases OMV biogenesis remains elusive. However, transcriptome analyses revealed that{Delta} dma2 has decreased expression of select polysaccharide utilization loci (PULs) that primarily target host-associated glycans. Follow-up comparative proteomics showed that the PUL repertoire was most impacted in the OMV fraction. In vitro growth assessments showed that{Delta} dma2 exhibits delayed growth in the presence of select host-associated glycans. Colonization studies in mice revealed that{Delta} dma2 is outcompeted by the wild-type in the gut, which indicates that dma2 is a key determinant of colonization fitness in Bt. Altogether, these findings expand our knowledge of the Dma familys role in OMV biogenesis and demonstrates their importance in Bacteroides physiology. ImportanceDual membrane-spanning anti-sigma factors (Dma) are a novel class of regulatory system found solely amongst Bacteroidota. Previous studies have demonstrated the role of Dma1 in vesiculation, but the overall role of the Dma family in Bacteroides physiology remains poorly understood. Here, we demonstrate that Dma2 modulates vesiculation and regulates the expression of select polysaccharide utilization loci (PULs) that target host-associated glycans. In vivo studies revealed that Dma2 is an important fitness determinant when competing against kin bacteria. This work begins characterizing the multifaceted involvement of Dma2 in OMV biogenesis, PUL regulation, and colonization fitness.

microbiology↗

In situ architecture of the endosymbiont Wolbachia pipientis

Hidden within host cells, the endosymbiont Wolbachia pipientis is the most prevalent bacterial infection in the animal kingdom. Scientific breakthroughs over the past century yielded fundamental mechanisms by which Wolbachia controls arthropod reproduction to shape dynamic ecological and evolutionary trajectories. However, the structure and spatial organization of symbiont machineries that underpin intracellular colonization and orchestrate maternal inheritance remain unknown. Here, we used cryo-electron tomography to directly image the nanoscale architecture of bacterial tools deployed for host manipulation and germline transmission. We discovered that Wolbachia assembles multiple structures at the host-endosymbiont interface including a filamentous ladder-like framework hypothesized to serve as a specialized motility mechanism that enables bacterial translocation to specific host cell compartments during embryogenesis and somatic tissue dissemination. In addition, we present the first in situ structure of the Rickettsiales vir homolog type IV secretion system (rvh T4SS). We provide evidence that the rvh T4SS nanomachine exhibits architectural similarities to the pED208-encoded T4SS apparatus including the biogenesis of rigid conjugative pili extending hundreds of nanometers beyond the bacterial cell surface. Coupled with integrative structural modeling, we demonstrate that in contrast to canonical T4SS architectures, the -proteobacterial T4SS outer membrane complex assembles a periplasmic baseplate structure predicted to comprise VirB9 oligomers complexed with cognate VirB10 subunits that form extended antennae projections surrounding the translocation channel pore. Collectively, these studies provide an unprecedented view into Wolbachia structural cell biology and unveil the molecular blueprints for architectural paradigms that reinforce ancient host-microbe symbioses.

microbiology↗

The Disruption and Normalization of Cortical Language Network Dynamics After Post-Stroke White Matter Disconnection

The human language network undergoes reorganization across different spatiotemporal scales, limited by its fixed structural neurobiological foundations. Although stroke often damages white matter, its effect on temporary language network reorganization is not fully understood. This study examined longitudinal behavioral and resting-state fMRI data from post-stroke patients with exclusive subcortical lesions at three time points: two weeks (n = 38), three months (n = 29), and one year (n = 27). Patients showed mild to moderate language impairments during the acute phase, which improved within three months. The extent of disconnection in several left-hemispheric white matter tracts was negatively associated with language deficits. Healthy controls (HC, n = 25) exhibited domain-segregation dynamics in the cortical language network, limited by the underlying white matter pathways. In patients, severe, state- and track-specific network disruptions were observed in the acute phase, characterized by hypo- and hyper-connectivity and abnormal topological features. As language recovery progressed, connectivity patterns began to return to normal, resembling those of HC, and the domain-segregation dynamics reappeared. These results deepen our understanding of structure-function coupling and indicate significant post-lesional plasticity within the cortical language network.

neuroscience↗

A maize near-isogenic line population designed for gene discovery and characterization of allelic effects

In this study we characterized a panel of 1,264 maize near-isogenic lines (NILs), developed from crosses between 18 diverse inbred lines and the recurrent parent B73, referred to as nested NILs (nNILs). 884 of the nNILs were genotyped using genotyping-by-sequencing (GBS). Subsequently, 24 of these nNILs, and all the parental lines, were re-genotyped using a high-density SNP chip. A novel pipeline for calling introgressions, which does not rely on knowing the donor parent of each nNIL, was developed based on a hidden Markov model (HMM) algorithm. By comparing the introgressions detected using GBS data with those identified using chip data, we optimized the HMM parameters for analyzing the entire nNIL population. A total of 2,972 introgressions were identified across the 884 nNILs. Individual introgression blocks ranged from 21 bp to 204 Mbp, with an average size of 17 Mbp. By comparing SNP genotypes within introgressed segments to the known genotypes of the donor lines we determined that in about one third of the lines, the identity of the donors did not match expectation based on their pedigrees. We characterized the entire nNIL population for three foliar diseases. Using these data, we mapped a number of quantitative trait loci (QTL) for disease resistance in the nNIL population and observed extensive variation in effects among the alleles from different donor parents at most QTL identified. This population will be of significant utility for dissecting complex agronomic traits and allelic series in maize. Significance StatementThe study reports the characterization of a publicly available population of 1,264 maize near-isogenic lines largely derived from a single recurrent parent and 18 donor lines. This population is likely to be of significant utility for the characterization of allelic series at loci of interest.

plant biology↗

The connectional diaschisis and normalization of cortical language network dynamics after basal ganglia and thalamus stroke

Stroke affecting the basal ganglia and thalamus can lead to language deficits. In addition to the lesions direct impact on language processing, connectional diaschisis involving cortical-subcortical interactions also plays a critical role. This study investigated connectional diaschisis using the "dynamic meta-networking framework of language" in patients with basal ganglia and thalamus stroke, analyzing longitudinal resting-state fMRI data collected at 2 weeks (n = 32), 3 months (n = 19), and one year post-stroke (n = 23). As expected, we observed dynamic cortico-subcortical interactions between cortical language regions and subcortical regions in healthy controls (HC, n = 25). The cortical language network exhibited dynamic domain-segregation patterns in HCs, severely disrupted in the acute phase following stroke. The connectional diaschisis manifested as dual effects characterized by both hypo- and hyper-connectivity, which positively and negatively correlated with language deficits, respectively. State-specific changes in nodal and topological properties were also identified. Throughout language recovery, cortical language network dynamics gradually normalized toward sub-optimal domain-segregation patterns, accompanied by the normalization of nodal and topological properties. These findings underscore the crucial role of cortico-subcortical interactions in language processing.

neuroscience↗

Glia-derived secretory fatty acid binding protein Obp44a regulates lipid storage and efflux in the developing Drosophila brain

Glia derived secretory factors play diverse roles in supporting the development, physiology, and stress responses of the central nervous system (CNS). Through transcriptomics and imaging analyses, we have identified Obp44a as one of the most abundantly produced secretory proteins from Drosophila CNS glia. Protein structure homology modeling and Nuclear Magnetic Resonance (NMR) experiments reveal Obp44a as a fatty acid binding protein (FABP) with a high affinity towards long-chain fatty acids in both native and oxidized forms. Further analyses demonstrate that Obp44a effectively infiltrates the neuropil, traffics between neuron and glia, and is secreted into hemolymph, acting as a lipid chaperone and scavenger to regulate lipid and redox homeostasis in the developing brain. In agreement with this essential role, deficiency of Obp44a leads to anatomical and behavioral deficits in adult animals and elevated oxidized lipid levels. Collectively, our findings unveil the crucial involvement of a noncanonical lipid chaperone to shuttle fatty acids within and outside the brain, as needed to maintain a healthy brain lipid environment. These findings could inspire the design of novel approaches to restore lipid homeostasis that is dysregulated in CNS diseases.

developmental biology↗

Pan-cancer characterization and clinical outcome of ecDNA-enhancer mediated transcriptional dysregulation

Extrachromosomal circular DNAs (ecDNAs) are extrachromosomal circular DNA elements harboring enhancers that can function as mobile transcriptional enhancers to promote oncogene amplification in diverse human cancers. However, little is known about the mechanism how ecDNA and relevant enhancers influence the transcription control in different cancers. Here, we performed a comprehensive pan-cancer analysis to explore the potential transcriptional regulatory network between ecDNA and enhancer, and the association with clinical outcomes in different human cancers. Firstly, we identified 18,385 enhancers on ecDNA in 1,921 samples of 20 TCGA tumors. By integrating corresponding RNA-seq data, we found that the expression levels of enhancer RNAs (eRNAs) were significantly different between ecDNA regions and corresponding linear chromosomes. This suggested that enhancers on ecDNA may employ eRNA to perform transcriptional regulation. Furthermore, we identified enhancer co-amplification with oncogenes and found that enhancers on ecDNA significantly affect the expression of co-amplified cancer genes and consequently influence the survival of cancer patients. In addition, we found that, compared to corresponding linear chromosomes, enhancers on ecDNA generally have lower levels of methylation, which may be mainly caused by the enhancer co-amplification with oncogenes. Genome-wide analysis of open chromatin regions revealed significantly higher levels of chromatin accessibility and certain chromosomal preferences in ecDNA regions comparing corresponding linear chromosomes. Moreover, we found that the downregulation of antigen presentation genes and the suppression of antigen presentation pathways may cause the tumor immune evasion mediated by ecDNA. Finally, we identified tumor-infiltrating activated mast cells in ecDNA-positive patients, which are associated with poorer prognosis. In summary, through pan-cancer analysis, we illustrate the characteristics and regulatory mechanisms of ecDNA and its enhancers in cancers, providing insights for future cancer treatment.

bioinformatics↗

Identification and functional analysis of extrachromosomal circular DNA in plasma extracellular vesicles of liver failure patients

Withdrawal statementThe authors have withdrawn their manuscript owing to having identified certain issues with the current representation of the data in the manuscript after performing further analyses of the bioinformatics data from their eccDNA sequencing results. Therefore, the authors do not wish this work to be cited as reference for the project. A revised and corrected version will be submitted in the future. If you have any questions, please contact the corresponding authors.

genomics↗

Site-specific Effector Protein Functionalization to Create Bead-based Avidity Model Systems

The cooperative effect of multiple affinity binding interactions creating a stable bond, known as avidity, is a universal biological phenomenon seen in diverse systems. For example, avidity based biomolecular interactions are particularly important in assessing the potency of potential drugs such as monoclonal antibodies, chimeric antigen receptor (CAR) T-cell, or Natural Killer, cells to treat cancer or engineering microbes with cell surface immobilized enzyme complexes for consolidated bioprocessing (CBP) of cellulosic biomass to fuels and chemicals. However, predicting or measuring avidity based on in vitro single affinity interactions with non-complexed protein-ligand binding model systems has limitations and often fails to describe the avidity effects observed in vivo with cell surface complexed proteins interacting with multivalent ligands at solid interfaces. Acoustic force spectroscopy (AFS) based assays have recently emerged as a reliable method for direct avidity measurements, expressed as adhesion or rupture forces, which positively correlate with in vivo avidity interactions. However, to better understand and model avidity, in particular for cell-cell interactions and to correlate it with classical binding affinity, a cell mimetic model system with controlled avidity-related properties is needed. Here, we present a method for producing such a cell mimetic model system using "effector beads" that can be used in AFS-based avidity assays or any other bead-based avidity assay. The protein of interest is heterologously expressed and biotinylated in vivo in E. coli, purified, and subsequently tethered with streptavidin coated micron-sized beads to create effector beads. Our experimental results, combined with simulations of the multivalent binding phenomena, demonstrate the dependency of bead rupture force on its receptor protein surface density and force loading rate as well as the intrinsic kinetic binding parameters of the protein-ligand system of interest. These insights provide valuable information for designing future effector bead assays and cell avidity measurements for screening and characterization purposes for diverse applications.

bioengineering↗

eccDNA Atlas: a comprehensive resource of eccDNA catalog

Extrachromosomal circular DNA (eccDNA) represents a large category of nonmitochondrial and nonplasmid circular extrachromosomal DNA playing an indispensable role in various aspects such as tumorigenesis, immune responses, liquid biopsy, etc. However, characteristic and functions of eccDNA are fragmented, hiding behind abundant literatures and massive whole-genome sequencing (WGS) data, which have not been sufficiently used for identification of eccDNAs. Therefore, establishing an integrated repository portal is essential for identifying and analyzing eccDNAs. Here, we developed eccDNA Atlas (http://lcbb.swjtu.edu.cn/eccDNAatlas), a user-friendly database of eccDNAs that aims to provide a high-quality and integrated resource for browsing, searching and analyzing eccDNAs from multiple species. eccDNA Atlas currently containing 630,434 eccDNAs and 7,774 ecDNAs manually curated from literatures and 1,105 ecDNAs predicted by AmpliconArchitect based on WGS data involved in 66 diseases, 57 tissue and 319 cell lines. The content of each eccDNA entry included multiple aspects such as sequence, disease, function, characteristic, validation strategies, etc. Furthermore, abundant annotations and analyzing utilities were provided to explore existed eccDNAs in eccDNA Atlas or user-defined eccDNAs including oncogenes, typical enhancers, super enhancers, gene expression, survival, and genome visualization. Based on these resources, eccDNA Atlas will significantly improve our understanding of eccDNAs and serve as an important catalyst for future research of eccDNAs.

bioinformatics↗

A novel non-invasive biomarker based on oral microbiome dysbiosis for detection of Community-Acquired Pneumonia

BackgroundEarly diagnosis of pathogenic bacteria is crucial for the treatment of community-acquired pneumonia (CAP), but conventional diagnostics are limited by sampling difficulties. Oral microbiota has also been explored as a noninvasive biomarker of lung diseases, but its role in CAP has been neglected. We aimed to investigate whether the oral bacteria can be novel non-invasive biomarkers for CAP. MethodsOral swab samples were collected from 29 patients with CAP and 26 healthy volunteers and characterized based on clinical parameters and 16S rRNA profiling of oral bacteria. A predict functional profiling was performed for the functional and metabolic changes in oral microbial communities. ResultsOral microbial of patients with CAP had a lower diversity than healthy group. And the dominant bacteria were Streptococcus, Prevotella and Neisseria in CAP. Higher abundance of Prevotella (particularly Prevotella_melaninogenica), Veillonella and Campylobacter, and lower abundance of Neisseria and Fusobacterium were detected in CAP group. Analysis of the functional potential of oral microbiota demonstrated that the pathway involving infectious disease was overrepresented in the CAP groups relative to that in the healthy controls. ConclusionsOral microbial dysbiosis was found in patients with CAP, supporting the use of this non-invasive specimen for biomarkers of CAP. HighlightsO_LIOral microbial diversity was significantly lower in community-acquired pneumonia (CAP) patients than healthy controls. C_LIO_LIGenera Neisseria and Fusobacterium were decreased, while genera Prevotella, Veillonella and Campylobacter were increased in CAP versus healthy controls. C_LIO_LIOral microbiota-based biomarkers can serve as a promising non-invasive tool for the detection of CAP. C_LI

microbiology↗

Efficiently, accurately, intelligently dissecting bamboo: characteristic of vascular bundle in Phyllostachys

A comprehensive understanding of vascular bundles is the key to elucidate the excellent intrinsic mechanical properties of bamboo. This research aims to investigate the gradient distribution of fiber volume fraction and the gradient changes in the shape of vascular bundles along the radial axis in Phyllostachys. We constructed a universal transfer-learning-based vascular bundle detection model with high precision of up to 96.97%, which can help to acquire the characteristics of vascular bundles quickly and accurately. The total number of vascular bundles, total fiber sheath area, the length, width and area of fiber sheath of individual vascular bundles within the entire cross-section were counted, and the results showed that these parameters had a strongly positive linear correlation with the outer circumference and wall thickness of bamboo culms, but the fiber volume fraction (around 25.5 %) and the length-to-width ratio of the vascular bundles (around 1.226) were relatively constant. Furthermore, we layered the cross section of bamboo according to the wall thickness finely and counted the characteristics of vascular bundle in each layer. The results showed that the radial distribution of fiber volume fraction decreased exponentially, the radial distribution of the length-to-width ratio of vascular bundle decreased quadratically, the radial distribution of the width of vascular bundle increased linearly. The trends of the gradient change in vascular bundles characteristics were found highly consistent among 29 bamboo species in Phyllostachys. One sentence summaryA universal vascular bundle detection model can efficiently dissect vascular bundles in Phyllostachys, and the radial gradient change of vascular bundles in cross-section are found highly consistent.

plant biology↗

Renal Interstitial Cells Promote Nephron Regeneration by Secreting Prostaglandin E2

In organ regeneration, progrnitor and stem cells reside in their native microenvironment, which provides dynamic physical and chemical cues essential to their survival, proliferation and differentiation. However, what kind of cells provide a native microenvironment for renal progenitor cells has not been clarified. Here, single-cell sequencing of zebrafish kidney revealed that fabp10 was a marker of renal interstitial cells (RICs), and the Tg(fabp10a:GFP) transgenic line can specifically label RICs in zebrafish kidney. The formation of RICs and nephrons are closely accompanied during nephron regeneration. RICs form a network to wrap the renal progenitor cell aggregates. RICs in close contact with cell aggregates express cyclooxygenase 2 and secrete prostaglandin 2 (PGE2). Inhibiting PGE2 production prevented nephrogenesis by reducing the proliferation and differentiation of progenitor cell aggregates. PGE2 promoted maturation of the nephron by activating the WNT signaling pathway in progenitor cell aggregates in cooperation with Wnt4a. These findings suggest that RICs provide a necessary microenvironment for rapid nephrogenesis during nephron regeneration.

developmental biology↗