Biology subjects

wang, j.

Publications and source records attributed to wang, j..

At least 19 recordsLinked to original sources

bioRxiv2026

Socio-demographic gradients in traumatic brain injury disability, severity and nutrition: a two-level analysis of the Global Burden of Disease Study 2023 and NHANES 2011-2014

Traumatic brain injury (TBI) is among the most consequential non-fatal outcomes of trauma, yet how its burden, severity and nutritional context are patterned by socio-demographic development remains incompletely characterised. We addressed this question at two levels. Using the Global Burden of Disease (GBD) Study 2023, we quantified the socio-demographic gradients of TBI disability across the five socio-demographic index (SDI) quintiles and characterised the severity composition of the TBI disability burden, its 1990-2023 trend and its cause-specific structure. Using pooled NHANES 2011-2014, we then examined, at the individual level, how reported TBI history among US adults aged 40 years and older varied by income, education, health insurance and food security, and whether dietary differences between adults with and without a TBI history persisted after socio-economic adjustment. The age-standardised TBI disability rate was almost twice as high in the high SDI quintile as in the low SDI quintile (113.68 versus 57.55 per 100,000 in 2023), a gap essentially unchanged since 1990. Moderate or severe injuries accounted for 72.5% of the TBI disability burden in the high SDI quintile versus 84.0-84.6% in the other four quintiles, rising in every quintile between 1990 and 2023. Among US adults, reported TBI history rose with educational attainment (11.9% below high school versus 17.3% above) and was most common in very food-insecure households (23.4%; adjusted odds ratio 1.71, 95% confidence interval 1.39-2.09); income showed no unadjusted gradient but a negative association after mutual adjustment. Unadjusted dietary differences between adults with and without a TBI history largely attenuated after socio-economic adjustment, with only fibre density remaining marginally lower (-0.35 g/1,000 kcal, 95% confidence interval -0.64 to -0.06). The moderate or severe share of the disability burden is a tractable, mortality-free monitoring indicator for injury prevention, and nutritional risk among food-insecure TBI survivors warrants clinical attention.

neuroscience↗

bioRxiv2026

Disease stage-sensitive MFSD2A-caveolae axis insigates hippocampal blood-brain barrier disruption in Alzheimer's disease

Blood-brain barrier (BBB) malfunction contributes to pathophysiology of Alzheimer's disease (AD), yet the mechanisms that confer hippocampal endotheliocytes vulnerability remain unclear. Here we identify loss of endothelial major facilitator superfamily domain-containing protein 2A (MFSD2A), a suppressor of caveolae-mediated transcytosis, as an early and hippocampus-specific feature of AD-associated vascular impairment. In post-mortem human AD brains, reduction in hippocampal MFSD2A was accompanied with increased levels of caveolin-1 and perivascular albumin extravasation. Analysis of human single-nucleus transcriptomic data further demonstrated that vascular expression of MFSD2A declined during transition from mild cognitive impairment to established AD. In APP/PS1 mice, MFSD2A loss occurred early in hippocampal microvessels and coincided with disproportionately high hippocampal BBB leakage and reductions in GLUT1 and claudin-5, despite broader amyloid deposition throughout other brain regions. Restoration of endothelial MFSD2A using an AAV-BR1-based vascular vector during early stage of amyloid pathology, reduced albumin extravasation and preserved GLUT1 and claudin-5. Early intervention also reduced amyloid plaque burden and plaque-associated neuritic dystrophy, whereas this treatment during established amyloid pathology, although modifying selected endothelial markers, failed to reverse BBB leakage, amyloid pathology, or cognitive impairment. Sustained MFSD2A restoration from the early disease stage provided the greatest protection, preserving hippocampal BBB integrity, reducing amyloid and neuritic pathology, improving long-term potentiation and ameliorating spatial learning and memory deficits. These findings define endothelial MFSD2A loss as a disease stage-sensitive mechanism of hippocampal BBB vulnerability and highlight the MFSD2A-caveolae axis as a therapeutic target for early-stage AD.

neuroscience↗

bioRxiv2026

A Unified Structure-Based Deep-Learning Framework for High-Throughput Screening of Protein-Binding RNAs

Protein-RNA interactions regulate diverse biological processes and are increasingly exploited in therapeutic RNA discovery, but accurate inferences of nucleotide preferences and reliable structure prediction remain challenging. Here, we present PRIS, a unified structure-based deep-learning framework that combines two complementary components: PRISeq for nucleotide probability estimation at each RNA position and PRIScore for residue-nucleotide distance prediction to discriminate native-like from incorrect poses. Both share a feature extractor that integrates an Anti-Symmetric Graph Attention Network (A-GAT) with sparse k-Maximum Inner Product (k-MPI) attention to capture long-range interactions across large graphs. PRIScore improves the selection of native-like protein-RNA predictions generated by AlphaFold3, achieving a top-1 success rate of 81.91% on a docking benchmark, compared to 79.26% for AlphaFold3. The selected structures are then fed into PRISeq, which infers position-specific binding preferences and screens RNA libraries. On a PWM benchmark, PRISeq achieved a mean absolute error (MAE) of 0.75, outperforming FoldX, Rosetta-based scoring functions, and NA-MPNN. In virtual screening against MS2 protein, PRISeq screens 129,248 RNA hairpins within 11.95 seconds, achieving the highest EF0.5% of 14.40, approximately double the best baseline. PRIS also effectively enriches active aptamers against NELF-E and GFP while preserving sequence diversity. By integrating structure selection with binding-preference inference, PRIS provides an efficient framework for large-scale RNA library screening and aptamer design.

bioinformatics↗

bioRxiv2026

Hierarchical Gating of Cortical Population Dynamics Drives Pain

The prefrontal cortex and anterior cingulate cortex are key cortical hubs for pain regulation, yet the functional hierarchy between them remains unclear. We examined how the prelimbic cortex (PL) to ACC pathway regulates nociceptive processing and pain behavior in freely moving rats across synaptic, cellular, and network levels. Activation of the PL to ACC pathway reduced aversion to both evoked and spontaneous pain, whereas inhibition increased pain aversion, indicating that this circuit exerts tonic modulatory control. Meanwhile, ex vivo electrophysiology revealed that PL inputs recruit local ACC interneurons to produce feedforward inhibition of ACC pyramidal neurons. At the cellular level, in vivo microendoscopic calcium imaging showed that optogenetic activation of PL axon terminals suppresses nociceptive-evoked activity of ACC pyramidal neurons. At the network level, PL activation reduced pain-induced excitability while centralizing nociceptive information flow within the ACC, resulting in a gated, low output population state. Overall, these findings identify a hierarchically organized cortical circuit that tonically controls pain related sensory and affective experience.

neuroscience↗

bioRxiv2025

Analysis of Nutritional Components in Brown Sugar and Its Effects on Anti-fatigue, Alleviation of Qi Deficiency and Blood Stasis, and Antioxidant Effects

Brown sugar (BS), Red granulated sugar (RGS) and White sugar(WS) are three key sweeteners and food additives in China. Notably, BS possesses significant nutritional value and has been widely used in Chinese medicine for its supportive therapeutic properties.This study evaluated the anti-fatigue, the amelioration of qi deficiency and blood stasis, as well as the antioxidant activities of these sugars using a zebrafish model. BS and RGS demonstrated significantly greater efficacy than WS in terms of both anti-fatigue effects and amelioration of qi Deficiency and blood stasis in the zebrafish model. Antioxidant assays revealed that BS, RGS, and WS (500 g/mL) significantly enhanced superoxide dismutase (SOD) activity in zebrafish embryos compared with the control group. Furthermore, the mineral composition of sugar were determined. Nine mineral elements--potassium (K), calcium (Ca), sodium (Na), magnesium (Mg), iron (Fe), zinc (Zn), copper (Cu), phosphorus (P), and selenium (Se)--were analyzed. BS exhibited markedly higher concentrations of P, Ca, Fe, and Mg than RGS and WS, while selenium (detected at 50 mg/kg) was exclusively detected in BS. Intriguingly, RGS contained four-fold higher potassium levels than BS. Total polyphenol content, quantified by Folin-Ciocalteu assay, was 4.35 g/kg in BS and 1.53 g/kg in RGS, with no detectable polyphenols in WS.

biochemistry↗

bioRxiv2025

Class A PBPs reinforce the septal cell wall following initial synthesis by SEDS-bPBP pairs during bacterial cytokinesis

Bacterial cytokinesis requires the coordinated action of septal peptidoglycan (PG) synthases to ensure efficient and accurate septum formation. Two major types of synthases contribute: SEDS-bPBP and bifunctional class A PBPs (aPBPs). How their activities are organized in space and time has remained unclear. Using Deinococcus radiodurans, which often contains both constricting and closed septa in the same cell, we show that septal PG synthesis proceeds through distinct steps at different regions. Primary synthesis at the leading edge by SEDS-bPBP pairs drives constriction, whereas aPBPs act later at the lagging edge and in closed septa to thicken the wall, enhance cross-linking, and reinforce septal integrity. At the single-molecule level, both synthase types move directionally to perform processive PG synthesis at distinct sites. We also observed spatiotemporal separation of SEDS-bPBP and aPBP synthases in Staphylococcus aureus, suggesting that secondary septal PG synthesis is a conserved mechanism securing successful cytokinesis.

microbiology↗

bioRxiv2025

BLTP2 orchestrates lysobisphosphatidic acid synthesis and exosome biogenesis via SCAMP3-dependent ER contacts in tumorigenesis

Multivesicular bodies (MVBs) contain intraluminal vesicles (ILVs) designated for degradation in lysosomes or release as exosomes for cell-to-cell communication. The mechanisms governing ILV/exosome formation are not fully understood. Here, we show that the integral endoplasmic reticulum (ER) membrane protein bridge-like lipid transfer protein 2 (BLTP2; KIAA0100) is indispensable in ILV/exosome formation and that secretory carrier membrane protein 3 (SCAMP3) recruits BLTP2 to ER-MVB membrane contact sites (MCSs) in a Rab5-dependent manner. Our results indicate that this recruitment is hindered by NEDD4-mediated ubiquitination of SCAMP3. Depletion of BLTP2 was found to impede ILV/exosome formation and selectively diminish the levels of cone-shaped phospholipids, including bis(monoacylglycero)phosphate (BMP) and the BMP precursor phosphatidylglycerol (PG) within endosomes. BLTP2 knockout also hampered cell proliferation and tumorigenicity, which could be restored to a significant extent by supplementation with exosomes from wild-type cells. Since BLTP2 is associated with acute monocytic leukemia and is highly expressed in breast cancer, our findings suggest that BLTP2 transfers the BMP/LBPA precursor PG to MVBs for BMP/LBPA synthesis and promotes ILV/exosome formation at SCAMP3-dependent ER-MVB MCSs, a process crucial for cell proliferation and tumorigenesis.

cell biology↗

bioRxiv2025

Dissecting organoid-bacteria interaction highlights decreased contractile force as a key factor for heart infection

Bacterial endocarditis is a fatal cardiovascular disease exacerbated by weakened heart contraction, yet the direct impact of cardiac contractility on bacterial adhesion remains elusive. Here, we present a novel quantitative physics model integrating finite element analysis and live-cell imaging to uncover their strong correlation. Using this model, we quantified the real-time force magnitude generated by organoid-type cardiac microtissue derived from healthy donors and dilated cardiomyopathy patients - mimicking normal and suppressed heart contractility, respectively - to the approaching bacteria in a real fluidic system. The data revealed that weakened cardiac contractility facilitated bacterial invasion of the myocardium. Verifying this finding in a mouse transverse aortic constriction model demonstrated that increasing heart contraction efficiently mitigated bacterial invasion, with a 25% increase in heart contractility reducing endocarditis risk by 80%. Our findings demonstrate that patient-derived cardiac organoids provide a physiologically relevant platform for studying bacterial infections in vitro, offering high clinical fidelity. This platform establishes a valuable tool for drug screening and the development of novel therapeutic strategies.

bioengineering↗

bioRxiv2025

Peritoneal cavity-derived GATA6+ macrophages inhibit fibrosis through IL33 in endometrium

Macrophages exhibit a high degree of plasticity and play pivotal roles both in the normal physiological cycle of the endometrium and in its regeneration following injury. Although some new subsets of endometrial macrophages have been identified, their origins and functions remain to be further explored. In this study, we employed single-cell sequencing to analyze the endometrium of patients with normal endometrium and intrauterine adhesion (IUA) caused by injury. We identified a unique subset of macrophages distinguished by the expression of GATA6, a marker indicative of cavity macrophages. We verified that these GATA6+ macrophages were large peritoneal macrophages (LPMs) that migrated from the peritoneal cavity to the injured endometrium. Upon activation by injured endometrium, these LPMs demonstrated increased expression of Interleukin-33 (IL33), mediated by the Lars-Fos signaling axis, which interacts with the IL33 enhancer. Moreover, our studies revealed that IL33 derived from LPMs inhibited the differentiation of endometrial stromal cells (ESCs) into myofibroblasts, a critical step in the development of endometrial fibrosis. Furthermore, we confirmed the inhibitory effect occurred through the binding of IL33 to the ST2 receptor on ESCs, leading to the upregulation of JMJD3 and subsequent suppression of myofibroblast differentiation. Our findings highlight the essential role of LPMs in promoting endometrial repair and inhibiting fibrosis in IUA. Significance StatementThis study reveals the presence of a unique population of macrophages within the endometrium, originating from large peritoneal macrophages (LPMs), that are pivotal in endometrial repair. This finding offers new insights into the plasticity of macrophages and their potential therapeutic applications in treating endometrial fibrotic disorders.

immunology↗

bioRxiv2025

Electrospinning of hydroxypropyl chitosan nanofibers for bone regeneration application

To study the effect of electrospinning nanofiber mats synthesized using hydroxypropyl chitosan in conjugation with poly (vinyl alcohol) on the osteogenesis in MC3T3 cell, we fabricated different ratios of hydroxypropyl chitosan (HPCH) and poly (vinyl alcohol) to electrospin the nanofiber mats, the mechanical and physical properties of nanofiber mats were tested by using SEM, FT-IR and conventional methods. Then the effect of the electrospinning mats on osteogenesis in MC3T3 cell were evaluated by Alizarin Red stain, ALP stain and expression of relevant genes. We found that the nanofiber mats fabricated by hydroxypropyl chitosan (50%) and poly (vinyl alcohol)(50%) can induce osteoblast differentiation apparently in MC3T3 cell.

biochemistry↗

bioRxiv2024

Ligand-independent c-Met activation by HHLA2 drives hepatocellular carcinoma and predicts c-MET inhibitor efficacy

The HGF/c-Met signaling pathway facilitates the initiation, progression, and metastasis of hepatocellular carcinoma (HCC). c-Met activation, however, is complex and not solely dependent on HGF, hindering targeted therapy development. This study identifies a critical oncogenic role for HHLA2, a B7 family member, in HCC and highlights its potential as a therapeutic target. We demonstrate that HHLA2 directly interacts with and activates c-Met through N-glycosylation, triggering sustained signaling and promoting aggressive HCC features. Mechanistically, we identified the pro-tumorigenic role of HHLA2 required downstream upregulation of MMP9 and VEGFA, both implicated in tumor progression. In multiple mouse models, HHLA2 overexpression accelerated tumor progression, metastasis, and reduced liver NK cell infiltration, all of which were reversed by c-Met inhibition. In a cohort of 176 HCC patients, HHLA2 expression strongly correlated with c-Met phosphorylation, advanced tumor stage, and poor prognosis. Importantly, HHLA2 expression predicted sensitivity to c-Met inhibitors in cell lines and patient-derived organoids and could be detected in patient serum, suggesting its potential as a prognostic biomarker. Collectively, our findings reveal an HHLA2-mediated mechanism of c-Met activation and provide a strong rationale for targeting the HHLA2-c-Met axis as a novel therapeutic strategy, with HHLA2 serving as a potential prognostic biomarker. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=173 SRC="FIGDIR/small/622557v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@8b10dforg.highwire.dtl.DTLVardef@b43dorg.highwire.dtl.DTLVardef@394c4aorg.highwire.dtl.DTLVardef@1bfbc8c_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

Osterix Facilitates Osteocytic Communication by Targeting Connexin43

Osteocytes, terminal-differentiated cells in bone, are now considered as more pivotal regulators of mature bone homeostasis than other bone cells, since they constitute 90- 95% of the bone cell population. Given their non-migratory nature within the mineralized matrix, their unique dendrites are crucial for cell-to-cell communication in response to both intracellular and extracellular stimuli, such as bone fracture or mechanical load. Here, we showed that Osterix (Osx), usually recognized as a specific doorkeeper for osteoblast differentiation during new bone formation marked by collagen type I 1 (Col11), was unexpectedly co-expressed with Col11 in osteocytes within the cortical bone of mice. Deleting Osx in Col11-positive osteocytes disrupted cortical bone structure and osteocytic dendrites in mice, thus impairing transcellular fluid flow and intercellular communication. Conversely, overexpression of Osx in osteocytes enhanced these processes. Furthermore, we identified Connexin43, a critical protein of gap junction channel, was a direct transcriptional target of Osx in regulating dendrites of osteocytes. Pharmacological restoration of Connexin43 levels rescued the dysfunction in Osx-deficient osteocytes both in vitro and in vivo. Taken together, this work demonstrated Osxs distinct role in osteocyte function through maintaining intercellular signaling, which broadened the current understanding of its role in Col11-positive bone cells, extending beyond osteoblasts and bone mineralization, offering new insights into bone diseases such as fracture nonunion or disuse osteoporosis.

cell biology↗

bioRxiv2024

ORMDL3 restrains type-I interferon signaling and anti-tumor immunity by promoting RIG-I degradation

Mounting evidence has demonstrated the genetic association of ORMDL3 (ORMDL Sphingolipid Biosynthesis Regulator 3) gene polymorphisms with bronchial asthma and a diverse set of inflammatory disorders. However, its role in type I interferon (IFN) signaling remains poorly defined. Herein, we report that ORMDL3 is a negative modulator of the type I IFN signaling by interacting with MAVS (Mitochondrial Antiviral Signaling protein) and subsequently promoting the proteasome-mediated degradation of RIG-I (Retinoic Acid-Inducible Gene I). Immunoprecipitation coupled with mass spectrometry (IP-MS) assays uncovered that ORMDL3 binds to USP10 (Ubiquitin-Specific Protease 10), which forms a complex with and stabilizes RIG-I through decreasing its K48-linked ubiquitination. ORMDL3 thus disrupts the interaction between USP10 and RIG-I, thereby promoting RIG-I degradation. Additionally, subcutaneous syngeneic tumor models in C57BL/6 mice revealed that inhibition of ORMDL3 enhances anti-tumor efficacy by augmenting the proportion of cytotoxic CD8 positive T cells and IFN production in the tumor microenvironment (TME). Collectively, our findings reveal the pivotal roles of ORMDL3 in maintaining antiviral innate immune responses and anti-tumor immunity.

molecular biology↗

bioRxiv2024

Gradual labeling with fluorogenic probes for MINFLUX nanoscopy of densely packed structures

Single-molecule localization in densely packed structures represents a formidable challenge in nanoscopy. Here we develop a gradual labeling method with fluorogenic probes for MINFLUX nanoscopy (GLF-MINFLUX), with which individual proteins in packed structures can be sequential illuminated and quantitatively localized at the nanoscale solely by adjusting probe concentration. With a 1.7-fold localization precision improvement and 2.2-fold faster acquisition, GLF-MINFLUX enables dual-channel nanoscale imaging of densely neuronal microtubules and microfilaments, and three-dimensional quantitative mapping of individual TOM20 proteins in mitochondrial clusters.

biophysics↗

bioRxiv2024

The molecular basis of pine wilt disease resistance in Pinus massoniana

Pine wilt disease (PWD), caused by the pine wood nematode (PWN) Bursaphelenchus xylophilus, results in significant economic and ecological damage to Pinus forests and plantations worldwide. Pinus massoniana is the primary host of PWD in southern China, but its response to the PWN remains largely unstudied. Previously, we observed PWD in a P. massoniana nursery that contained over 71 commonly used cultivars. Through field phenotyping, we identified two groups of PWN resistant cultivars. Resistant cultivars (RC) exhibited very low PWN carrying amounts (PCA) and had relatively low mortality, and tolerant cultivars (TC) had high PCA but low mortality. In this study, we confirmed via PWN inoculation assays that the resistant and tolerant cultivars had lower mortality rates, 10% and 11%, respectively, than other cultivars (which had a mortality rate of 83.3%). The RC had a PCA that was significantly lower than that of other cultivars, while the TC exhibited a higher PCA. To explore the molecular mechanisms underlying the response of P. massoniana to PWN, the transcriptome and metabolome of the above cultivars were profiled by high throughput sequencing. As no reference genome is available for P. massoniana, we generated a new full-length transcriptome library with iso-seq. Using the transcriptome and metabolome from different P. massoniana cultivars inoculated with PWN, we found three major PWD resistance strategies. 1) The common response strategy involved three important molecular pathways. First, synthesis of indole-3-acetic acid (IAA) and abcisic acid (ABA) were suppressed during PWN invasion, thus suppressing the synthesis of polysaccharides (especially myo-inositol and trehalose) and (-)-riboflavin through ABC transporters. Second, by inhibiting aspartic acid, the synthesis of arginine and proline through APS5 (aspartate aminotransferase 5) were suppressed. Third, by reducing cysteine, GERD (germacrene D synthase) was up-regulated, and sesquiterpenoid and triterpenoid metabolites were accumulated to resist PWN invasion. 2) The most effective resistance strategy involved the accumulation of reactive oxygen species (ROS), which enhanced jasmonic acid (JA) accumulation and highly induced the expression of chitinase, thus improving resistance to PWN. 3) The tolerance strategy involved the induction of phosphatidylcholine, which promoted flavonoid and anthocyanin synthesis via LPIN (phosphatidate phosphatase), LOX2S (lipoxygenase), and LOX1_5 (linoleate 9S-lipoxygenase), thus significantly inhibiting the pathogenicity of the PWN but not the PCA. These results illustrate the molecular mechanisms by which P. massoniana cultivars resist or tolerate PWN and are of great significance in the prevention and control of PWD.

plant biology↗

bioRxiv2021

Quantifying microbial associations of dissolved organic matter under global change

Microbes play a critical role in regulating the size, composition, and turnover of dissolved organic matter (DOM), which is one of the largest pools of carbon in aquatic ecosystems. Global change may alter DOM-microbe associations with implications for biogeochemical cycles, although disentangling these complex interactions remains a major challenge. Here we develop a framework called Energy-Diversity-Trait integrative Analysis (EDTiA) to examine the associations between DOM and bacteria along temperature and nutrient gradients in a manipulative field experiment on mountainsides in contrasting subarctic and subtropical climates. In both study regions, the chemical composition of DOM correlated with bacterial communities, and was primarily controlled by nutrients and to a lesser degree by temperature. At a molecular-level, DOM-bacteria associations depended strongly on the molecular traits of DOM, with negative associations indicative of decomposition as molecules are more biolabile. Using bipartite networks, we further demonstrated that negative associations were more specialized than positive associations indicative of DOM production. Nutrient enrichment promoted specialization of positive associations, but decreased specialization of negative associations particularly at warmer temperatures in subtropical climate. These global change drivers influenced specialization of negative associations most strongly via molecular traits, while both molecular traits and bacterial diversity similarly affected positive associations. Together, our framework provides a quantitative approach to understand DOM-microbe associations and wider carbon cycling across scales under global change.

ecology↗

bioRxiv2021

Heterogeneity and molecular programming of progenitors for motor neurons and oligodendrocytes

The pMN domain is a restricted domain in the ventral spinal cords, defined by the expression of olig2 gene. The fate determination of pMN progenitors is highly temporally and spatially regulated, with motor neurons and oligodendrocyte progenitor cells (OPCs) developing sequentially. Insight into the heterogeneity and molecular programs of pMN progenitors is currently lacking. With the zebrafish model, we identified multiple states of neural progenitors using single-cell sequencing: proliferating progenitors, common progenitors for both motor neurons and OPCs, and restricted precursors for either motor neurons or OPCs. We found specific molecular programs for neural progenitor fate transition, and manipulations of representative genes in the motor neuron or OPC lineage confirmed their critical role in cell fate determination. The transcription factor NPAS3 is necessary for the development of the OPC lineage and can interact with many known genes associated with schizophrenia. Deciphering progenitor heterogeneity and molecular mechanisms for these transitions will elucidate the formation of complex neuron-glia networks in the central nervous system during development, and understand the basis of neurodevelopmental disorders.

neuroscience↗

bioRxiv2020

Single-cell transcriptional atlas of the Chinese horseshoe bat (Rhinolophus sinicus) provides insight into the cellular mechanisms which enable bats to be viral reservoirs

Bats are a major "viral reservoir" in nature and there is a great interest in not only the cell biology of their innate and adaptive immune systems, but also in the expression patterns of receptors used for cellular entry by viruses with potential cross-species transmission. To address this and other questions, we created a single-cell transcriptomic atlas of the Chinese horseshoe bat (Rhinolophus sinicus) which comprises 82,924 cells from 19 organs and tissues. This atlas provides a molecular characterization of numerous cell types from a variety of anatomical sites, and we used it to identify clusters of transcription features that define cell types across all of the surveyed organs. Analysis of viral entry receptor genes for known zoonotic viruses showed cell distribution patterns similar to that of humans, with higher expression levels in bat intestine epithelial cells. In terms of the immune system, CD8+ T cells are in high proportion with tissue-resident memory T cells, and long-lived effector memory nature killer (NK) T-like cells (KLRG1, GZMA and ITGA4 genes) are broadly distributed across the organs. Isolated lung primary bat pulmonary fibroblast (BPF) cells were used to evaluate innate immunity, and they showed a weak response to interferon {beta} and tumor necrosis factor- compared to their human counterparts, consistent with our transcriptional analysis. This compendium of transcriptome data provides a molecular foundation for understanding the cell identities, functions and cellular receptor characteristics for viral reservoirs and zoonotic transmission.

cell biology↗