Biology subjects

Wu, X.

Publications and source records attributed to Wu, X..

At least 487 records · Page 27Linked to original sources

bioRxiv2021

A B cell actomyosin arc network couples integrin co-stimulation to mechanical force-dependent immune synapse formation

B-cell activation and immune synapse (IS) formation with membrane-bound antigens are actin-dependent processes that scale positively with the strength of antigen-induced signals. Importantly, ligating the B-cell integrin, LFA-1, with ICAM-1 promotes IS formation when antigen is limiting. Whether the actin cytoskeleton plays a specific role in integrin-dependent IS formation is unknown. Here we show using super-resolution imaging of mouse primary B cells that LFA-1: ICAM-1 interactions promote the formation of an actomyosin network that dominates the B-cell IS. This network is created by the formin mDia1, organized into concentric, contractile arcs by myosin 2A, and flows inward at the same rate as B-cell receptor (BCR): antigen clusters. Consistently, individual BCR microclusters are swept inward by individual actomyosin arcs. Under conditions where integrin is required for synapse formation, inhibiting myosin impairs synapse formation, as evidenced by reduced antigen centralization, diminished BCR signaling, and defective signaling protein distribution at the synapse. Together, these results argue that a contractile actomyosin arc network plays a key role in the mechanism by which LFA-1 co-stimulation promotes B-cell activation and IS formation.

immunology↗

bioRxiv2021

CureSCi Metadata Catalog - Making sickle cell studies findable

ObjectivesTo adopt the FAIR principles (Findable, Accessible, Interoperable, Reusable) to enhance data sharing, the Cure Sickle Cell Initiative (CureSCi) MetaData Catalog (MDC) was developed to make Sickle Cell Disease (SCD) study datasets more Findable by curating study metadata and making them available through an open-access web portal. MethodsStudy metadata, including study protocol, data collection forms, and data dictionaries, describe information about study patient-level data. We curated key metadata of 16 SCD studies in a three-tiered conceptual framework of category, subcategory, and data element using ontologies and controlled vocabularies to organize the study variables. We developed the CureSCi MDC by indexing study metadata to enable effective browse and search capabilities at three levels: study, Patient-Reported Outcome (PRO) Measures, and data element levels. ResultsThe CureSCi MDC offers several browse and search tools to discover studies by study level, PRO Measures, and data elements. The "Browse Studies," "Browse Studies by PRO Measures," and "Browse Studies by Data Elements" tools allow users to identify studies through pre-defined conceptual categories. "Search by Keyword" and "Search Data Element by Concept Category" can be used separately or in combination to provide more granularity to refine the search results. This resource helps investigators find information about specific data elements across studies using public browsing/search tools, before going through data request procedures to access controlled datasets. The MDC makes SCD studies more Findable through browsing/searching study information, PRO Measures, and data elements, aiding in the reuse of existing SCD data.

bioinformatics↗

bioRxiv2021

Kindlin-2 preserves integrity of the articular cartilage to protect against osteoarthritis

Osteoarthritis (OA) is an aging-related degenerative joint disease, which has no cure partly due to limited understanding of its pathological mechanism(s). Here we report that the focal adhesion protein Kindlin-2, but not Kindlin-1 or -3, is highly expressed in articular chondrocytes of the hyaline cartilage, which is dramatically decreased in the degenerated articular cartilage of aged mice and patients with OA. Inducible deletion of Kindlin-2 in chondrocytes at adult stage leads to spontaneous OA and much severe OA lesions in the mice receiving the surgery of destabilization of the medial meniscus. Mechanistically, Kindlin-2 deficiency promotes mitochondrial oxidative stress and activates Stat3 in articular chondrocytes, leading to Runx2-mediated chondrocyte hypertrophic differentiation and catabolism. In vivo, systemic pharmacological blockade of Stat3 activation or genetic ablation of Stat3 in chondrocytes reverses aberrant accumulation of Runx2 and ECM-degrading enzymes and limits OA deteriorations caused by Kindlin-2 deficiency. Furthermore, genetic inactivation of Runx2 in chondrocytes reverses structural changes and OA lesions caused by Kindlin-2 deletion without down-regulating p-Stat3 in articular chondrocytes. Of translational significance, intraarticular injection of Kindlin-2-expressing adeno-associated virus decelerates progression of aging- and instability-induced knee joint OA in mice. Collectively, we identify a novel pathway comprising of Kindlin-2, Stat3 and Runx2 in articular chondrocytes responsible for maintaining integrity of the articular cartilage and define a potential therapeutic target for OA.

pathology↗

bioRxiv2021

Cryo-EM structure determination of small proteins by nanobody-binding scaffolds (Legobodies)

We describe a general method that allows structure determination of small proteins by single-particle cryo-electron microscopy (cryo-EM). The method is based on the availability of a target-binding nanobody, which is then rigidly attached to two scaffolds: (1) a Fab-fragment of an antibody directed against the nanobody, and (2) a nanobody-binding protein A fragment fused to maltose binding protein and Fab-binding domains. The overall ensemble of [~]120 kDa, called Legobody, does not perturb the nanobody-target interaction and facilitates particle alignment in cryo-EM image processing. The utility of the method is demonstrated for the KDEL receptor, a 23 kDa membrane protein, resulting in a map at 3.2[A] overall resolution with density sufficient for de novo model building, and for the 22 kDa RBD of SARS-CoV2 spike protein, resulting in a map at 3.6 [A] resolution that allows analysis of the binding interface to the nanobody. The Legobody approach thus overcomes the current size limitations of cryo-EM analysis.

biochemistry↗

bioRxiv2021

Brain Laterality Dynamics Support Human Cognition

Hemispheric lateralization constitutes a core architectural principle of human brain organization underlying cognition, often argued to represent a stable, trait-like feature. However, emerging evidence underlines the inherently dynamic nature of brain networks, in which time-resolved alterations in functional lateralization remain uncharted. Integrating dynamic network approaches with the concept of hemispheric laterality, we map the spatiotemporal architecture of whole-brain lateralization in a large sample of high-quality resting-state fMRI data (N=991, Human Connectome Project). We reveal distinct laterality dynamics across lower-order sensorimotor systems and higher-order associative networks. Specifically, we expose two aspects of the laterality dynamics: laterality fluctuations, defined as the standard deviation of laterality time series, and laterality reversal, referring to the number of zero-crossings in laterality time series. These two measures are associated with moderate and extreme changes in laterality over time, respectively. While laterality fluctuations depict positive association with language function and cognitive flexibility, laterality reversal shows a negative association with the same neurocognitive factors. These opposing interactions indicate a dynamic balance between intra- and inter-hemispheric communication, i.e., segregation and integration of information across hemispheres. Furthermore, in their time-resolved laterality index, the default-mode and language networks correlate negatively with visual/sensorimotor and attention networks, indicating flexible while parallel processing capabilities that are linked to better out-of-scanner cognitive performance. Finally, the laterality dynamics correlate with regional metabolism and structural connectivity and showed significant heritability. Our results provide insights into the adaptive nature of the lateralized brain and new perspectives for future studies of human cognition, genetics and brain disorders.

neuroscience↗

bioRxiv2021

The first crested duck genome reveals clues to genetic compensation and crest cushion formation

The Chinese crested (CC) duck is a unique indigenous waterfowl breed with a phenotypic crest trait that affects its high survival rate. Therefore, the CC duck is an ideal model to investigate the genetic compensation response to maintain genetic stability. In the present study, we first generated a chromosome-level genome of CC ducks. Comparative genomics revealed genes related to tissue repair, immune function, and tumors were under strong positive selection, which suggested that these adaptive changes might enhance cancer resistance and immune response to maintain the genetic stability of CC ducks. We sub-assembled a Chinese spot-billed duck genome and detected genome-assembled structure variants among three ducks. Functional analysis revealed that a large number of structural variants were related to the immune system, which strongly suggests the occurrence of genetic compensation in the anti-tumor and immune systems to further support the survival of CC ducks. Moreover, we confirmed that the CC duck originated from the mallard ducks. Finally, we revealed the physiological and genetic basis of crest traits and identified a causative mutation in TAS2R40 that leads to crest formation. Overall, the findings of this study provide new insights into the role of genetic compensation in adaptive evolution.

genomics↗

bioRxiv2021

A drug candidate for treating adverse reactions caused by pathogenic antibodies inducible by COVID-19 virus and vaccines

In a recent study, we reported that certain anti-spike antibodies of COVID-19 and SARS-CoV viruses can have a pathogenic effect through binding to sick lung epithelium cells and misleading immune responses to attack self-cells. We termed this new pathogenic mechanism "Antibody Dependent Auto-Attack" (ADAA). This study explores a drug candidate for prevention and treatment of such ADAA-based diseases. The drug candidate is a formulation comprising N-acetylneuraminic acid methyl ester (NANA-Me), an analog of N-acetylneuraminic acid. NANA-Me acts through a unique mechanism of action (MOA) which is repairment of the missing sialic acid on sick lung epithelium cells. This MOA can block the antibodies binding to sick cells, which are vulnerable to pathogenic antibodies. Our in vivo data showed that the formulation significantly reduced the sickness and deaths caused by pathogenic anti-spike antibodies. Therefore, the formulation has the potential to prevent and treat the serious conditions caused by pathogenic antibodies during a COVID-19 infection. In addition, the formulation has potential to prevent and treat the adverse reactions of COVID-19 vaccines because the vaccines can induce similar antibodies, including pathogenic antibodies. The formulation will be helpful in increasing the safety of the vaccines without reducing the vaccines efficacy. Compared to existing antiviral drugs, the formulation has a unique MOA of targeting receptors, broad spectrum of indications, excellent safety profile, resistance to mutations, and can be easily produced.

microbiology↗

bioRxiv2021

EpicPCR-Directed Cultivation of a Candidatus Saccharibacteria Symbiont Reveals a Type IV Pili-dependent Epibiotic Lifestyle

Candidate phyla radiations (CPR), accounting for a major microbial supergroup with remarkably small genomes and reduced sizes, are widely distributed yet mostly uncultured. Limited culture and its obligate reliance upon other bacteria hindered investigation of their lifestyles. In this work we isolated a CPR bacterium, TM7i, with its host Leucobacter aridocollis J1, by combination of Emulsion, Paired Isolation and Concatenation PCR (epicPCR) detection and filtrate co-culture. Genomic profiling of TM7 genomes and microscopic investigation of TM7i-J1 symbiosis suggest the conservation of type IV pili and a pili-dependent lifestyle of TM7. Further, we observed twitching motility of TM7i mediated by pili and its role played in the interaction with its host. Our results shed a light on the lifestyle about this enigmatic bacterial radiation, which may also be adopted by other CPR organisms. The epicPCR-directed isolation method underlines high efficiency of CPR bacteria isolation and thus may be used in other symbiotic or epibiotic microorganisms.

microbiology↗

bioRxiv2021

A SUBTILISIN-LIKE SERINE PROTEASE1 (OsSUBSrP1), plays an important role in the wax and cutin pathway, is essential for panicle development in rice

Panicle degeneration is a severe physiological defect and causes reduction in grain yield. In this study, we characterized and presented the functional analysis of our previously reported mutant apa1331 (apical panicle abortion1331) that showed apical spikelet degeneration. The anthers from the apical spikelets of apa1331 were degenerated, pollen-less and showed lack of cuticle formation. Transverse sections showed normal meiosis till stage 5-6, however, defects in post-meiotic microspore development were found at stage 8-9 in apa1331. Measurement of wax and cutin analysis showed a significant reduction in anthers of apa1331 compared to Wildtype (WT). Quantification of H2O2 and MDA has indicated the excessive ROS (reactive oxygen species) in apa1331. Trypan blue staining, and TUNEL assay revealed cell death and excessive DNA fragmentation in apa1331. Map-based cloning and Mutmap analysis identified a candidate gene (LOC_Os04g40720) that is a SUBTILISIN-LIKE SERINE PROTEASE (OsSUBSrP1) which harbored an SNP (A>G) in apa1331. CRISPR-mediated knock-out lines of OsSUBSrP1 displayed spikelet degeneration comparable to apa1331. Global gene expression analysis revealed a significant downregulation of wax and cutin biosynthesis genes e.g., OsWDA1, OsMS2 and OsCER4 in apa1331. Our study reports the novel role of SUBSrP1 in ROS-mediated cell death in panicle development. Highlights1. OsSUBSrP1 plays an important role in maintaining ROS-mediated programmed cell death. 2. OsSUBSrP1 is essential for apical spikelet development. 3. OsSUBSrP1 regulates the expression of wax and cutin biosynthesis pathway genes.

molecular biology↗

bioRxiv2021

Microglia and border-associated mouse macrophages maintain their embryonic origin during Alzheimers disease

Brain microglia and border-associated macrophages (BAMs) display distinct spatial, developmental, and phenotypic features. Although at steady-state, the origins of distinct brain macrophages are well-documented, the dynamics of their replenishment in neurodegenerative disorders remain elusive, particularly for disease-associated microglia (DAMs) and BAMs. In this study, we conducted a comprehensive fate-mapping analysis of murine microglia and BAMs and their turnover kinetics during Alzheimers disease (AD) progression. We used a novel inducible AD mouse model to investigate the contribution of bone marrow cells to the pool of foetal-derived brain macrophages during the development of AD. We demonstrated that microglia and DAMs remain a remarkably stable embryonic-derived population even during the progression of AD pathology, indicating that neither parenchymal macrophage subpopulation originates from, nor are replenished by, monocytes. At the border-associated brain regions, bona fide CD206+ BAMs are minimally replaced by monocytes, and their turnover rates are not accelerated by AD. In contrast, all other myeloid cells are swiftly replenished by bone marrow progenitors. This information further elucidates the turnover kinetics of these cells not only at steady-state, but also in neurodegenerative diseases, which is crucial for identifying potential novel therapeutic targets. Impact statementInducible fate-mapping analysis demonstrates that neither microglia, disease-associated microglia nor border-associated macrophages are replenished by bone marrow-derived cells in Alzheimers disease.

immunology↗

bioRxiv2021

Proximity-dependent biotinylation to elucidate the interactome of TNK2 non-receptor tyrosine kinase

Non-receptor tyrosine kinases represent an important class of signaling molecules which are involved in driving diverse cellular pathways. Although, the large majority have been well-studied in terms of their protein-binding partners, the interactomes of some of the key non-receptor tyrosine kinases such as TNK2 (also known as activated Cdc42-associated kinase 1 or ACK1) have not been systematically investigated. Aberrant expression and hyperphosphorylation of TNK2 has been implicated in a number of cancers. However, the exact proteins and cellular events that mediate phenotypic changes downstream of TNK2 are unclear. Biological systems that employ proximity-dependent biotinylation methods, such as BioID, are being increasingly used to map protein-protein interactions as they provide increased sensitivity in discovering interaction partners. In this study, we employed BioID coupled to the biotinylation site identification technology (BioSITe) method that we recently developed to perform molecular mapping of intracellular proteins associated with TNK2. We also employed stable isotope labeling with amino acids in cell culture (SILAC) to quantitatively explore the interactome of TNK2. By performing a controlled comparative analysis between full-length TNK2 and its truncated counterpart, we were not only able to confidently identify site-level biotinylation of previously well-established TNK2 binders and substrates such as NCK1, NCK2, CTTN, STAT3, but also discover several novel TNK2 interacting partners. We validated TNK2 interaction with one of the novel TNK2 interacting protein, clathrin interactor 1 (CLINT1), using immunoblot analysis. Overall, this work reveals the power of the BioSITe method coupled to BioID and highlights several molecules that warrant further exploration to assess their functional significance in TNK2-mediated signaling.

cancer biology↗

bioRxiv2021

Transcription factor-like 5 is a potential DNA/RNA-binding protein essential for maintaining male fertility in mice.Running title: Tcfl5 is haploinsufficient in vivo

Tissue-specific transcription factors often play key roles in the development of specific cell lineages. Transcription factor-like 5 (TCFL5) is a testis-specific protein that contains the basic helix-loop-helix domain, although the in vivo functions of TCFL5 remain unknown. Herein, we generated CRISPR/Cas9-mediated knockout mice to dissect the function of TCFL5 in mouse testes. Surprisingly, we found that it was difficult to generate homozygous mice with the Tcfl5 deletion since the heterozygous males (Tcfl5+/-) were infertile. We did, however, observe markedly abnormal phenotypes of spermatids and spermatozoa in the testes and epididymides of Tcfl5+/- mice. Mechanistically, we demonstrated that TCFL5 transcriptionally regulated a set of genes participating in male germ cell development, which we uncovered via RNA-sequencing and TCFL5 ChIP-sequencing. We also found that TCFL5 interacted with RNA-binding proteins (RBPs) that regulated RNA processing, and further identified the fragile X mental retardation gene 1, autosomal homolog (FXR1, a known RBP) as an interacting partner of TCFL5 that may coordinate the transition and localization of TCFL5 in the nucleus. Collectively, we herein report for the first time that Tcfl5 is haploinsufficient in vivo and hypothesize that TCFL5 may be a dual-function protein that mediates DNA and RNA to regulate spermatogenesis.

cell biology↗

bioRxiv2021

Timing of meristem initiation and maintenance determines the morphology of fern gametophytes

The alternation of generations in land plants occurs between the sporophyte phase and the gametophyte phase. The sporophytes of seed plants develop self-maintained, multicellular meristems, and these meristems determine plant architecture. The gametophytes of seed plants lack meristems and are heterotrophic. In contrast, the gametophytes of seed-free vascular plants, including ferns, are autotrophic and free-living, developing meristems to sustain their independent growth and proliferation. Compared to meristems in the sporophytes of seed plants, the cellular mechanisms underlying meristem development in fern gametophytes remain largely unknown. Here, using confocal time-lapse live imaging and computational segmentation and quantification, we determined different patterns of cell divisions associated with the initiation and proliferation of two distinct types of meristems in fern gametophytes. Our results reveal how the simple timing of a switch between two meristems has considerable consequences for the divergent gametophyte morphologies of two closely related ferns from Pteridaceae (Pteris and Ceratopteris). Our result provides evolutionary insight into the function and regulation of gametophyte meristems in seed-free vascular plants. HighlightLive-imaging of cell growth and division in apical initials and lateral meristems reveals that the timing of a switch between the two meristem identities drives morphology variation in fern gametophytes.

plant biology↗

bioRxiv2021

Profiling tumor immune microenvironment of non-small cell lung cancer using multiplex immunofluorescence

PurposeWe attempt to profile the tumor immune microenvironment (TIME) of non-small cell lung cancer (NSCLC) by multiplex immunofluorescence (MIF). Experimental DesignMIF test was performed on 681 NSCLC cases in our center between 2009 and 2011. The number, density, proportion and correlation of 26 types of immune cells in tumor nest and tumor stroma were evaluated. An unsupervised consensus clustering approach was utilized to identify robust clusters of patients. Immune-related risk score (IRRS) was constructed for prognosis prediction for disease-free survival (DFS). ResultsThe landscape of TIME was illustrated, revealing some close interactions particularly between intrastromal neutrophils and intratumoral regulatory T cells (Treg) (r2 = 0.439, P < 0.001), intrastromal CD4+CD38+ T cells and intrastromal CD20-positive B cells (r2 = 0.539, P < 0.001), and intratumoral CD8-positive T cells and intratumoral M2 macrophages expressing PD-L1 (r2 = 0.339, P < 0.001). Three immune subtypes correlated with distinct immune characteristics and clinical outcomes were identified. The immune-activated subtype had the longest DFS and demonstrated the highest infiltration of CD4-positive T cells and CD20-positive B cells. The immune-defected subtype had the highest levels of cancer stem cells and macrophages. The immune-exempted subtype had the highest levels of neutrophils and Treg. The IRRS based on six robust prognostic biomarkers showed potential ability for risk stratification (high vs. median vs. low) and prediction of five-year DFS rates (43.1% vs. 37.9% vs. 23.2%, P<0.001). ConclusionsOur study profiled the intricate and intrinsic structure of TIME in NSCLC, which showed potency in subtyping and prognostication. Translational RelevanceSignificant unmet need exists in understanding the tumor immune microenvironment (TIME) of non-small cell lung cancer (NSCLC) and its correlation with prognosis. In this retrospective cohort study (n = 681), we profiled the immune landscape of NSCLC in situ and identified a novel stratification of TIME by three immune subtypes: immune-activated, immune-exempted, and immune-defected using multiplex immunofluorescence for testing 26 kinds of immune cells. Each of the immune subtypes was correlated with distinct composition, spatial distribution, and functional orientation of immune cells, and accordingly indicating significantly different disease-free survival (DFS). Close interactions were observed for several kinds of immune cells, including neutrophils and regulatory T cells, CD4+CD38+ T cells and CD20-positive B cells, and CD8-positive T cells and M2 macrophages. We also developed the immune-related risk score (IRRS) with different immune characteristics based on six robust immune biomarkers in TIME and evaluated its role in risk stratification and prognosis prediction of DFS. This study might bring potential clinical implementations for the design of novel immunotherapies and the optimization of combined strategies.

cancer biology↗

bioRxiv2021

Comprehensive Analysis of Spatial Architecture in Primary Liver Cancer

Heterogeneity is the major challenge for cancer prevention and therapy. Here, we firstly constructed high-resolution spatial transcriptomes of primary liver cancers (PLCs) containing 84,823 spots within 21 tissues from 7 patients. The sequential comparison of spatial tumor microenvironment (TME) characteristics from non-tumor to leading-edge to tumor regions revealed that the tumor capsule potentially affects intratumor spatial cluster continuity, transcriptome diversity and immune cell infiltration. Locally, we found that the bidirectional ligand-receptor interactions at the 100 m wide cluster-cluster boundary contribute to maintaining intratumor architecture. Our study provides novel insights for diverse tumor ecosystem of PLCs and has potential benefits for cancer intervention.

cancer biology↗

bioRxiv2021

Building the cytokinetic contractile ring in an early embryo: initiation as clusters of myosin II, anillin and septin, and visualization of a septin filament network

The cytokinetic contractile ring (CR) was first described some 50 years ago, however our understanding of the assembly and structure of the animal cell CR remains incomplete. We recently reported that mature CRs in sea urchin embryos contain myosin II mini-filaments organized into aligned concatenated arrays, and that in early CRs myosin II formed discrete clusters that transformed into the linearized structure over time. The present study extends our previous work by addressing the hypothesis that these myosin II clusters also contain the crucial scaffolding proteins anillin and septin, known to help link actin, myosin II, RhoA, and the membrane during cytokinesis. Super-resolution imaging of cortices from dividing embryos indicates that within each cluster, anillin and septin2 occupy a centralized position relative to the myosin II mini-filaments. As CR formation progresses, the myosin II, septin and anillin containing clusters enlarge and coalesce into patchy and faintly linear patterns. Our super-resolution images provide the initial visualization of anillin and septin nanostructure within an animal cell CR, including evidence of a septin filament network. Furthermore, Latrunculin-treated embryos indicated that the localization of septin or anillin to the myosin II clusters in the early CR was not dependent on actin filaments. These results highlight the structural progression of the CR in sea urchin embryos from an array of clusters to a linearized purse string, the association of anillin and septin with this process, and provide, for the first time, the visualization of septin filament higher order structure in an animal cell CR.

cell biology↗

bioRxiv2021

Multiview super-resolution microscopy

We enhance the performance of confocal microscopy over imaging scales spanning tens of nanometers to millimeters in space and milliseconds to hours in time, improving volumetric resolution more than 10-fold while simultaneously reducing phototoxicity. We achieve these gains via an integrated, four-pronged approach: 1) developing compact line-scanners that enable sensitive, rapid, diffraction-limited imaging over large areas; 2) combining line-scanning with multiview imaging, developing reconstruction algorithms that improve resolution isotropy and recover signal otherwise lost to scattering; 3) adapting techniques from structured illumination microscopy, achieving super-resolution imaging in densely labeled, thick samples; 4) synergizing deep learning with these advances, further improving imaging speed, resolution and duration. We demonstrate these capabilities on more than twenty distinct fixed and live samples, including protein distributions in single cells; nuclei and developing neurons in Caenorhabditis elegans embryos, larvae, and adults; myoblasts in Drosophila wing imaginal disks; and mouse renal, esophageal, cardiac, and brain tissues.

bioengineering↗

bioRxiv2021

A transcriptomics-guided drug target discovery strategy identifies novel receptor ligands for lung regeneration

Currently, there is no pharmacological treatment targeting defective tissue repair in chronic disease. Here we utilized a transcriptomics-guided drug target discovery strategy using gene signatures of smoking-associated chronic obstructive pulmonary disease (COPD) and from mice chronically exposed to cigarette smoke, identifying druggable targets expressed in alveolar epithelial progenitors of which we screened the function in lung organoids. We found several drug targets with regenerative potential of which EP and IP prostanoid receptor ligands had the most significant therapeutic potential in restoring cigarette smoke-induced defects in alveolar epithelial progenitors in vitro and in vivo. Mechanistically, we discovered by using scRNA-sequencing analysis that circadian clock and cell cycle/apoptosis signaling pathways were enriched in alveolar epithelial progenitor cells in COPD patients and in a relevant model of COPD, which was prevented by PGE2 or PGI2 mimetics. Conclusively, specific targeting of EP and IP receptors offers therapeutic potential for injury to repair in COPD.

pharmacology and toxicology↗