Biology subjects

Zhang, Q.

Publications and source records attributed to Zhang, Q..

At least 451 records · Page 25Linked to original sources

bioRxiv2023

Single-cell transcriptomic landscape deciphers novel olfactory neuroblastoma subtypes and intratumoral heterogeneity

Olfactory neuroblastoma (ONB) is an uncommon malignant tumor known to originate from the olfactory epithelial. The complex tumor ecosystem of this pathology remained unclear. Here, we explored the cellular components with ONB tumors based on scRNA profiles of 96,325 single-cells derived from 10 tumors and 1 olfactory mucosa sample. We discovered 11 major cell types, including 6 immune cell, 3 stromal cell subtypes and epithelial cluster in the tumor microenvironment (TME), and identified 5 common expression programs from malignant epithelial cells. We analyzed subclusters of TME and the interactions among different cell types in the TME. An innovative three-classification of ONB was established via scRNA analysis. Markers for categorizing tumor samples into new subtypes were elucidated. Different responses towards certain chemotherapy regimens could be inferred according to the molecular features of three tumor types. Relative abundance of immunosuppressive TAMs indicated the benefits of immunotherapies targeting myeloid cells.

cancer biology↗

bioRxiv2023

Membrane-dependent actin polymerization mediated by the Legionella pneumophila effector protein MavH

L. pneumophila propagates in eukaryotic cells within a specialized niche, the Legionella-containing vacuole (LCV). The infection process is controlled by over 330 effector proteins delivered through the type IV secretion system. In this study, we report that the Legionella MavH effector harbors a lipid-binding domain that specifically recognizes PI(3)P (phosphatidylinositol 3-phosphate) and localizes to endosomes when ectopically expressed. We show that MavH recruits host actin capping proteins (CP) and actin to the endosome via its CP interacting (CPI) motif and WH2-like actin-binding domain, respectively. In vitro assays revealed that MavH stimulates robust actin polymerization only in the presence of PI(3)P-containing liposomes and the recruitment of CP by MavH negatively regulates F-actin density at the membrane. Furthermore, in L. pneumophila-infected cells, MavH can be detected around the LCV at the very early stage of infection. Together, our results reveal a novel mechanism of membrane-dependent actin polymerization catalyzed by MavH that may play a role at the early stage of L. pneumophila infection by regulating host actin dynamics.

molecular biology↗

bioRxiv2023

Caltubin regulates microtubule stability via Ca2+-dependent mechanisms favouring neurite regrowth

Microtubule regulation is highly controlled in nerve regeneration. Caltubin, a novel Lymnaea stagnalis protein, contains putative EF-hand calcium-binding motifs and promotes neuronal outgrowth in Lymnaea and mouse. Here, we generated cell-permeable caltubin proteins to investigate mechanisms underlying this effect. We observed increased neurite extension and outgrowth following injury in caltubin-treated mouse neurons compared to vehicle controls. Purified caltubin bound -tubulin between its L391-V405 amino acids and promoted microtubule assembly. Caltubin competitively inhibited binding of tubulin tyrosine ligase, which catalyzes tubulin retyrosination, and increased the ratio of detyrosinated to tyrosinated tubulin. Our crystal structure analysis confirmed that caltubin has four Ca2+-binding EF-hand motifs, like calmodulin but has distinct peptide binding domains. Our work suggests a unique Ca2+-dependent regulatory mechanism of microtubule assembly by caltubin. This may represent an essential mechanism of axonal regulation, which may optimize its activity in response to various calcium states, both physiological and following injury.

cell biology↗

bioRxiv2023

Adaptive optical two-photon fluorescence microscopy probes cellular organization of ocular lenses in vivo

The mammalian ocular lens is an avascular multicellular organ that grows continuously throughout life. Traditionally, its cellular organization is investigated using dissected lenses, which eliminates in vivo environmental and structural support. Here, we demonstrated that two-photon fluorescence microscopy (2PFM) can visualize lens cells in vivo. To maintain subcellular resolution at depth, we employed adaptive optics (AO) to correct aberrations due to ocular and lens tissues, which led to substantial signal and resolution improvements. Imaging lens cells up to 980 m deep, we observed novel cellular organizations including suture-associated voids, enlarged vacuoles, and large cavities, contrary to the conventional view of a highly ordered organization. We tracked these features longitudinally over weeks and observed the incorporation of new cells during growth. Taken together, non-invasive longitudinal in vivo imaging of lens morphology using AO 2PFM will allow us to directly observe the development or alterations of lens cellular organization in living animals.

bioengineering↗

bioRxiv2023

ProteoM enables deep and precise identification of peptides in data-dependent acquisition proteomics

Sensitive and reliable identification of proteins and peptides pertains the basis of proteomics. We introduce Mzion, a new database search tool for data-dependent acquisition (DDA) proteomics. Our tool utilizes an intensity tally strategy and achieves generally a higher performance in terms of depth and precision across twenty datasets, ranging from large-scale to single-cell proteomics. Compared to several other search engines, Mzion matches on average 20% more peptide spectra at tryptic enzymatic specificity and 80% more at no enzymatic specificity from six large-scale, global datasets. Mzion also identifies more phosphopeptide spectra that can be explained by fewer proteins, demonstrated by six large-scale, local datasets corresponding to the global data. Our findings highlight the potential of Mzion for improving proteomic analysis and advancing our understanding of protein biology.

bioinformatics↗

bioRxiv2023

An efficient context-aware approach for whole slide image classification

Computational pathology for gigapixel whole slide images (WSIs) at slide-level is helpful in disease diagnosis and remains challenging. We propose a context-aware approach termed WSI Inspection via Transformer (WIT) for slide-level classification via holistically modeling dependencies among patches on the WSI. WIT automatically learns feature representation of WSI by aggregating features of all image patches. We evaluate classification performance of WIT along with state-of-the-art baseline method. WIT achieved an accuracy of 82.1% (95% CI, 80.7% - 83.3%) in the detection of 32 cancer types on the TCGA dataset, 0.918 (0.910 - 0.925) in diagnosis of cancer on the CPTAC dataset and 0.882 (0.87 - 0.890) in the diagnosis of prostate cancer from needle biopsy slide, outperforming the baseline by 31.6%, 5.4% and 9.3%, respectively. WIT can pinpoint the WSI regions that are most influential for its decision. WIT represents a new paradigm for computational pathology, facilitating the development of effective tools for digital pathology.

pathology↗

bioRxiv2022

Human neurons lacking amyloid precursor protein exhibit cholesterol-associated developmental and presynaptic deficits

Amyloid precursor protein (APP) produces aggregable {beta}-amyloid peptides and its mutations are associated with familial Alzheimers disease, which makes it one of the most studied proteins. However, APPs role in the human brain remains unclear despite years of investigation. One problem is that most studies on APP have been carried out in cell lines or model organisms, which are physiologically different from human neurons in the brain. Recently, human induced neurons (hiNs) derived from induced pluripotent stem cells provide a practical platform for studying the human brain in vitro. Here, we generated APP-null iPSCs using CRISPR/Cas9 genome editing technology and differentiate them to matured human neurons with functional synapses using a two-step procedure. During hiN differentiation and maturation, APP-null cells exhibited less neurite growth and reduced synaptogenesis in serum-free but not serum-containing media. We have found that cholesterol (Chol) remedies those developmental defects in APP-null cells, consistent with Chols role in neurodevelopment and synaptogenesis. Phenotypic rescue was also achieved by co-culturing those cells with wildtype mouse astrocytes, suggesting that APPs developmental role is likely astrocytic. Next, we examined matured hiNs using patch-clamp recording and detected reduced synaptic transmission in APP-null cells. This change was largely due to decreased synaptic vesicle (SV) release and retrieval, which was confirmed by live-cell imaging using two SV-specific fluorescent reporters. Adding Chol shortly before stimulation mitigated the SV deficits in APP-null iNs, indicating that APP facilitates presynaptic membrane Chol turnover during SV exo-/endocytosis cycle. Taken together, our study in hiNs supports the notion that APP contributes to neurodevelopment, synaptogenesis and neurotransmission via maintaining brain Chol homeostasis. Given the vital role of Chol in the central nervous system, the functional connection between APP and Chol bears important implication in the pathogenesis of Alzheimers disease.

neuroscience↗

bioRxiv2022

MYSM1 co-activates ERα action via histone and non-histone deubiquitination to confer antiestrogen resistance in breast cancer

Endocrine resistance is a crucial challenge in estrogen receptor alpha (ER)-positive breast cancer (BCa) therapy. Aberrant alteration in modulation of E2/ER signaling pathway has emerged as the putative contributor for endocrine resistance in BCa. Thus, identification the efficient ER cofactor remains necessary for finding a potential therapeutic target for endocrine resistance. Herein, we have demonstrated that Myb like, SWIRM and MPN domains 1 (MYSM1) as a histone deubiquitinase is a novel ER co-activator with established Drosophila experimental model. Our results showed that MYSM1 participated in up-regulation of ER action via histone and non-histone deubiquitination. We provided the evidence to show that MYSM1 was involved in maintenance of ER stability via ER deubiquitination. Furthermore, silencing MYSM1 induced enhancement of histone H2A ubiquitination as well as reduction of histone H3K4me3 and H3Ac levels at cis regulatory elements on promoter of ER-regulated gene. In addition, MYSM1 depletion attenuated cell proliferation/growth in BCa-derived cell lines and xenograft models. Knockdown of MYSM1 increased the sensitivity of antiestrogen agents in BCa cells. MYSM1 was highly expressed in clinical BCa samples, especially in aromatase inhibitor (AI) non-responsive tissues. These findings clarify the molecular mechanism of MYSM1 as an epigenetic modifier in regulation of ER action and provide a potential therapeutic target for endocrine resistance in BCa.

cell biology↗

bioRxiv2022

An oral vaccine for SARS-CoV-2 RBD mRNA-bovine milk-derived exosomes induces a neutralizing antibody response in vivo

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) that causes the coronavirus disease 2019 (COVID-19) has presented numerous challenges to global health. The vaccines, including lipid-based nanoparticle mRNA, inactivated virus and recombined protein, have been used to prevent SARS-CoV-2 infections in clinics and are immensely helpful against the epidemic. Here, we first present an oral mRNA vaccine based on bovine milk-derived exosomes (milk-exos), which encodes the SARS-CoV-2 receptor binding domain (RBD) as an immunogen. The results indicated that RBD mRNA delivered by milk-derived exosomes can produce secreted RBD peptide in 293 cells in vitro and stimulated neutralizing antibodies against RBD in mice. These results indicated that bovine milk-derived exosome-based mRNA vaccine could serve as a new strategy for preventing SARS-CoV-2 infection. Meanwhile, it also can work as a new oral delivery system for mRNA. One Sentence SummaryOral SARS-CoV-2 mRNA vaccine based on bovine milk-derived exosomes can stimulate neutralizing antibodies in mice.

immunology↗

bioRxiv2022

Gut bacteria impact host uric acid burden and its association with atherosclerosis

Humans with metabolic and inflammatory diseases, including atherosclerosis harbor dysbiotic gut communities. However, the microbes and microbial pathways that influence disease progression remain largely undefined. Here, we show that variation in atherosclerosis burden is in part driven by the gut microbiota and it is associated with circulating levels of the proinflammatory molecule uric acid both in mice and humans. We identify bacterial taxa present in the gut spanning multiple phyla, including Bacillota (Firmicutes), Fusobacteriota and Pseudomonadota (Proteobacteria), that use uric acid and adenine- a key precursor of nucleic acids in intestinal cells, as carbon and energy sources anaerobically, and uncover a gene cluster encoding key steps of purine degradation that is widely distributed among gut dwelling bacteria. Furthermore, we demonstrate that colonization of germ-free mice with purine-degrading bacteria modulates levels of uric acid and other purines in the gut and systemically. Altogether this work demonstrates that gut microbes are important drivers of host global purine homeostasis and uric acid levels, and suggests that gut bacterial catabolism of purines may represent a novel mechanism by which the gut microbiome influences host health.

microbiology↗

bioRxiv2022

Mre11 liberates cGAS from nucleosome sequestration during tumorigenesis

Oncogene-induced replication stress generates endogenous DNA damage that activates cGAS/STING-mediated innate immune signaling and tumor suppression1-3. However, the mechanism for cGAS activation by endogenous DNA damage remains enigmatic, particularly given the constitutive inhibition of cGAS by high-affinity histone acidic patch (AP) binding4-10. Here we report an in vivo CRISPR screen that identified the DNA double strand break sensor Mre11 as a suppressor of mammary tumorigenesis induced by Myc overexpression and p53 deficiency. Mre11 antagonizes Myc-induced proliferation through cGAS/STING activation. Direct binding of the Mre11-Rad50-Nbn (MRN) complex to nucleosomes displaces cGAS from AP sequestration, which is required for DNA damage-induced cGAS mobilization and activation by cytosolic DNA. Mre11 is thereby essential for cGAS activation in response to oncogenic stress, cytosolic DNA transfection, and ionizing radiation. Furthermore, we show Mre11-dependent cGAS activation suppresses Myc-induced proliferation through ZBP1/RIPK3/MLKL-mediated necroptosis. In human triple-negative breast cancer, ZBP1 downregulation correlates with increased genome instability, decreased immune infiltration, and poor patient prognosis. These findings establish Mre11 as a critical link between DNA damage and cGAS activation that regulates tumorigenesis through ZBP1-dependent necroptosis. One-sentence summaryMre11 is required for cGAS activation during oncogenic stress and promotes ZBP1-dependent necroptosis.

cell biology↗

bioRxiv2022

Genetic Variants of Phospholipase C-γ 2 Confer Altered Microglial Phenotypes and Differential Risk for Alzheimers Disease

Genetic association studies have demonstrated the critical involvement of the microglial immune response in Alzheimers disease (AD) pathogenesis. Phospholipase C-gamma-2 (PLCG2) is selectively expressed by microglia and acts in many immune receptor signaling pathways. In AD, PLCG2 is induced uniquely in plaque-associated microglia. A genetic variant of PLCG2, PLCG2P522R, is a mild hypermorph that attenuates AD risk. We report the identification of a PLCG2 variant, PLCG2M28L, associated with loss-of-function and confers increased AD risk. PLCG2P522R attenuates disease in an amyloidogenic murine AD model, whereas PLCG2M28L exacerbates the plaque burden associated with altered phagocytosis and A{beta} clearance. The variants bidirectionally modulate disease pathology by inducing distinct transcriptional programs that identify microglial subpopulations associated with protective or detrimental phenotypes. In summary, these findings identify PLCG2M28L as a new AD risk variant and demonstrate that PLCG2 variants can differentially orchestrate microglial responses in AD pathogenesis that can be therapeutically targeted. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/519685v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@19f0aa6org.highwire.dtl.DTLVardef@74191eorg.highwire.dtl.DTLVardef@1d3a3forg.highwire.dtl.DTLVardef@db2a44_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIA genetic variant of PLCG2, M28L, is associated with an increased risk for Alzheimers disease (AD) C_LIO_LIIn an amyloidogenic AD mouse model, PLCG2M28L exacerbates disease pathogenesis C_LIO_LIConversely, PLCG2P522R, a protective PLCG2 variant, attenuates AD pathogenesis C_LIO_LIThe PLCG2 variants uniquely alter the microglial transcriptome and phenotypes C_LI

neuroscience↗

bioRxiv2022

Transcriptional lability of brain oxytocin receptor (Oxtr) generates diversity in brain OXTR distribution and social behaviors

Although oxytocin (OXT) exhibits a highly conserved neuroanatomical pattern among vertebrates, the distribution of OXT receptor (OXTR) in brain varies considerably across species and is associated with species-typical social behavior. To investigate the genomic basis of the phylogenetic plasticity in brain Oxtr expression and its social behavioral consequences, we generated transgenic mice carrying a bacteria artificial chromosome (BAC) harboring the entire prairie vole Oxtr locus and flanking intergenic regulatory regions. We established eight independent "volized" mouse lines expressing prairie vole Oxtr (pvOxtr). Strikingly, despite conserved Oxtr expression in mammary gland of all transgenic mouse lines, each line displayed a unique pattern of brain expression distinct from both mice and prairie voles. Together with topologically associating domain (TAD) structure analysis with mouse genome, our findings suggest that unlike Oxt, Oxtr expression patterns in brain, involve contributions of distal regulatory elements beyond the BAC insert. In contrast, Oxtr expression in peripheral tissues appears resistant to such distal influences. Moreover, the "volized" mouse lines with different brain Oxtr expression patterns showed differences in partner preference and maternal behaviors, providing direct functional evidence that variation in brain Oxtr expression can drive differences in social behaviors. We propose that brain Oxtr expression is transcriptionally sensitive to long-range interactions with distal genomic elements, rendering it more susceptible to diverse regulatory influences. This supports a model in which regulatory flexibility facilitates the evolutionary diversification of social behavior, while maintaining essential peripheral Oxtr expression.

neuroscience↗

bioRxiv2022

Mincle-GSDMD-mediated release of IL-1β containing small extracellular vesicles contributes to ethanol-induced liver injury

Background & AimsMacrophage inducible C-type lectin (Mincle) is expressed on Kupffer cells and senses ethanol-induced danger signals released from dying hepatocytes and promotes IL-1{beta} production. However, it remains unclear what and how ethanol-induced Mincle ligands activate downstream signaling events to mediate IL-1{beta} release and contribute to alcohol-associated liver disease (ALD). In this study, we investigated the association of circulating {beta}-glucosylceramide ({beta}-GluCer), an endogenous Mincle ligand, with severity of ALD and examined the mechanism by which {beta}-GluCer engages Mincle on Kupffer cells to release IL-1{beta} in the absence of cell death and exacerbates ALD. Approach and ResultsConcentrations of {beta}-GluCer were increased in serum of patients with severe AH and correlated with disease severity. Challenge of Kupffer cells with LPS and {beta}-GluCer induced formation of a Mincle and Gsdmd-dependent secretory complex containing chaperoned full-length GSDMD (Hsp90-CDC37-NEDD4) with polyubiquitinated pro-IL-1{beta} and components of the Casp8-NLRP3 inflammasome loaded as cargo in small extracellular vesicles (sEV). Gao-binge ethanol exposure to wild-type, but not Mincle-/- and Gsdmd-/-, mice increased release of IL-1{beta} containing sEVs from liver explant cultures. Myeloid-specific deletion of Gsdmd similarly decreased the formation of sEVs by liver explant cultures and protected mice from ethanol-induced liver injury. sEVs collected from ethanol-fed wild-type, but not Gsdmd-/-, mice promoted injury of cultured hepatocytes and, when injected into wild-type mice, aggravated Gao-binge ethanol-induced liver injury. Conclusion{beta}-GluCer functions as a DAMP activating Mincle-dependent GSDMD-mediated formation and release of IL-1{beta}-containing sEVs, which in turn exacerbate hepatocyte cell death and contribute to the pathogenesis of ALD.

immunology↗

bioRxiv2022

Statistical Inference of Enhancer-Gene Networks Reveals Pivotal Role of T-bet Expression Intensity for T Helper Cell Fate

Mammalian genomes harbor many more enhancers than genes, which greatly complicates the elucidation of cell-state-specific regulatory networks. Here, we developed a computational framework for learning enhancer-based gene networks from joint data on enhancer activity and transcript abundance. Dissecting the developmental plasticity of T helper (Th) cells with this approach, we uncovered a highly connected enhancer-gene network that supports graded Th-cell differentiation states, rather than mutual exclusivity of type-1 and type-2 immunity. Machine learning identifies a small number of regulatory enhancer types as network hubs. Hub enhancers in Th1 cells integrate as inputs the expression level of the master-regulator transcription factor, T-bet, and STAT signals governed by the cytokine environment. The quantitative balance between cell-intrinsic T-bet, driving phenotypic stability, and environmental cues enabling plasticity explains the heterogeneous reprogramming capacities of individual Th1 cells differentiating during natural infections in vivo. Moreover, we provide a framework for elucidating genome-scale regulatory networks based on enhancer activity.

systems biology↗

bioRxiv2022

Arabidopsis ORP2A positively regulates glucose signaling by interacting with AtRGS1 and promoting AtRGS1 degradation

Heterotrimeric GTP-binding proteins (G proteins) are a group of regulators essential for signal transmission into cells. AtRGS1 (Regulator of G protein Signaling 1) with intrinsic GTPase-accelerating protein (GAP) activity could suppress G protein and glucose signal transduction in Arabidopsis. However, how AtRGS1 activity is regulated is currently poor understood. Here we identified a knockout mutant orp2a-1 (oxysterol-binding protein (OSBP)-related protein 2A) which shows phenotypes similar to agb1-2 (arabidopsis g-protein beta 1). With overexpression of ORP2A, transgenic lines display short hypocotyl, hypersensitivity to sugar and lower intracellular AtRGS1 level than control. Consistently, ORP2A shows interaction with AtRGS1 in vitro and vivo. Tissue specificity of ORP2A with two alternative protein forms imply its functions in organ size and shape controlling. Bioinformatic data and phenotypes of orp2a-1, agb1-2 and double mutant reveal genetic interactions in the regulation of G protein signaling and sugar response between ORP2A and G{beta}. Both alternative splicing forms of ORP2A locate in the ER, PM (Plasma Membrane) and EPCS (ER-PM Contact Sites), and interact with VAP27-1 mediated by a FFAT-like motif in vivo and vitro. ORP2A also displays differential phosphatidyl phosphoinositide binding activity mediated by its PH domain in vitro. Taken together, it is suggested that Arabidopsis membrane protein ORP2A interacts with AtRGS1 and VAP27-1 to positively regulate G protein and sugar signaling by facilitating AtRGS1 degradation.

plant biology↗

bioRxiv2022

Retinal microvascular and neuronal pathologies probed in vivo by adaptive optical two-photon fluorescence microscopy

The retina, behind the transparent optics of the eye, is the only neural tissue whose physiology and pathology can be non-invasively probed by optical microscopy. The aberrations intrinsic to the mouse eye, however, prevent high-resolution investigation of retinal structure and function in vivo. Optimizing the design of a two-photon fluorescence microscope (2PFM) and sample preparation procedure, we found that adaptive optics (AO), by measuring and correcting ocular aberrations, is essential for resolving synapses and achieving three-dimensional cellular resolution in the mouse retina in vivo. Applying AO-2PFM to longitudinal retinal imaging in transgenic models of retinal pathology, we characterized microvascular lesions and observed microglial migration in a proliferative vascular retinopathy model, and found Lidocaine to effectively suppress retinal ganglion cell hyperactivity in a retinal degeneration model. Tracking structural and functional changes at high resolution longitudinally, AO-2PFM enables microscopic investigations of retinal pathology and pharmacology for disease diagnosis and treatment in vivo.

neuroscience↗

bioRxiv2022

Human Early Syncytiotrophoblasts Are Highly Susceptible to SARS-CoV-2 Infection

The ongoing and devastating pandemic of coronavirus disease 2019 (COVID-19) has led to a global public health crisis. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can potentially pose a serious risk to maternal and neonatal health. Cases of abnormal pregnancy and vertical transmission of SARS-CoV-2 from mother to foetus have been reported but no firm conclusions are drawn. Trophoblasts are the major constituents of the placenta to protect and nourish the developing foetus. However, direct in vivo investigation of trophoblasts susceptibility to SARS-CoV-2 and of COVID-19 and pregnancy is challenging. Here we report that human early syncytiotrophoblasts (eSTBs) are highly susceptible to SARS-CoV-2 infection in an angiotensin-converting enzyme 2 (ACE2)-dependent manner. From human expanded potential stem cells (hEPSCs), we derived bona fide trophoblast stem cells (TSCs) that resembled those originated from the blastocyst and the placenta in generating functional syncytiotrophoblasts (STBs) and extravillus trophoblasts (EVTs) and in low expression of HLA-A/B and amniotic epithelial (AME) cell signature. The EPSC-TSCs and their derivative trophoblasts including trophoblast organoids could be infected by SARS-CoV-2. Remarkably, eSTBs expressed high levels of ACE2 and produced substantially higher amounts of virion than Vero E6 cells which are widely used in SARS-CoV-2 research and vaccine production. These findings provide experimental evidence for the clinical observations that opportunistic SARS-CoV-2 infection during pregnancy can occur. At low concentrations, two well characterized antivirals, remdesivir and GC376, effectively eliminated infection of eSTBs by SARS-CoV-2 and middle east respiratory syndrome-related coronavirus (MERS-CoV), and rescued their developmental arrest caused by the virus infection. Several human cell lines have been used in coronavirus research. However, they suffer from genetic and/or innate immune defects and have some of the long-standing technical challenges such as cell transfection and genetic manipulation. In contrast, hEPSCs are normal human stem cells that are robust in culture, genetically stable and permit efficient gene-editing. They can produce and supply large amounts of physiologically relevant normal and genome-edited human cells such as eSTBs for isolation, propagation and production of coronaviruses for basic research, antivirus drug tests and safety evaluation.

cell biology↗