Biology subjects

Yang, Y.-G.

Publications and source records attributed to Yang, Y.-G..

6 recordsLinked to original sources

bioRxiv2023

STASCAN deciphers fine-resolution cell-distribution maps in spatial transcriptomics by deep learning

BackgroundThe spatial transcriptomics (ST) technologies have been widely applied to decode the spatial distribution of cells by resolving gene expression profiles in tissues. However, a fine-resolved spatial cell map is still limited by algorithmic tools and sequencing techniques. ResultsHere we develop a novel deep learning approach, STASCAN, which could define the spatial cellular distribution of both captured and uncharted areas by cell feature learning that combines gene expression profiles and histology images. STASCAN additionally adopts optional transfer learning and pseudo-labeling methods to improve the accuracy of the cell-type prediction from images. We have successfully applied STASCAN to enhance cell resolution, and revealed finer organizational structures across diverse datasets from various species and tissues generated from 10x Visium technology. STASCAN improves cell resolution of Schmidtea mediterranea datasets by six times and reconstructs more detailed 3D cell-type models. Furthermore, STASCAN could accurately pinpoint the boundaries of distinct cell layers in human intestinal tissue, specifically identify a micrometer-scale smooth muscle bundle structure in consistent with anatomic insights in human lung tissue, and redraw the spatial structural variation with enhanced cell patterns in human myocardial infarction tissue. Additionally, through STASCAN on embryonic mouse brain datasets generated by DBiT-derived MISAR-seq technology, the increased cellular resolution and distinct anatomical tissue domains with cell-type niches are revealed. Collectively, STASCAN is compatible with different ST technologies and has notable advantages in generating cell maps solely from histology images, thereby enhancing the spatial cellular resolution. ConclusionsIn short, STASCAN displays significant advantages in deciphering higher-resolution cellular distribution, resolving enhanced organizational structures and demonstrating its potential applications in exploring cell-cell interactions within the tissue microenvironment.

bioinformatics↗

bioRxiv2022

DNA damage-induced YTHDC1 O-GlcNAcylation promotes homologous recombination by enhancing N6-methyladenosine binding

N6-methyladenosine (m6A) is the most prevalent RNA modification, and its regulators include writers, readers and erasers. m6A is under stringent control and takes part in many biological events, but it is not known whether there is an interplay between m6A and glycosylation. Here we investigated an m6A reader, YTHDC1, which has been shown to be recruited to the DNA-RNA hybrid at DNA damage sites and regulate homologous recombination (HR) during DNA damage repair. We found that YTHDC1 is subject to O-linked {beta}-N-acetylglucosamine (O-GlcNAc) modification at Ser396 upon DNA damage, which is pivotal for YTHDC1 chromatin binding and ionization radiation induced foci (IRIF) formation. RNA immunoprecipitation (RIP) and molecular dynamics (MD) simulations indicate that O-GlcNAcylation is vital for YTHDC1 to bind with m6A RNA. Fluorescence recovery after photo bleaching (FRAP) analysis revealed that YTHDC1 O-GlcNAcylation is essential for DNA damage-induced YTHDC1-m6A condensate formation. We further demonstrate that YTHDC1 O-GlcNAcylation promotes HR-mediated DNA damage repair and cell survival, probably through recruitment of Rad51 to the damage sites. We propose that YTHDC1 O-GlcNAcylation is instrumental for HR and genome stability.

biochemistry↗

bioRxiv2021

Scrutiny of human lung infection by SARS-CoV-2 and associated human immune responses in humanized mice

There is an urgent need for animal models of COVID-19 to study immunopathogenesis and test therapeutic intervenes. In this study we showed that NSG mice engrafted with human lung (HL) tissue (NSG-L mice) could be infected efficiently by SARS-CoV-2, and that live virus capable of infecting Vero cells was found in the HL grafts and multiple organs from infected NSG-L mice. RNA-seq examination identified a series of differentially expressed genes, which are enriched in viral defense responses, chemotaxis, interferon stimulation, and pulmonary fibrosis between HL grafts from infected and control NSG-L mice. Furthermore, when infecting humanized mice with human immune system (HIS) and autologous HL grafts (HISL mice), the mice had bodyweight loss and hemorrhage and immune cell infiltration in HL grafts, which were not observed in immunodeficient NSG-L mice, indicating the development of anti-viral immune responses in these mice. In support of this possibility, the infected HISL mice showed bodyweight recovery and lack of detectable live virus at the later time. These results demonstrate that NSG-L and HISL mice are susceptible to SARS-CoV-2 infection, offering a useful in vivo model for studying SARS-CoV-2 infection and the associated immune response and immunopathology, and testing anti-SARS-CoV-2 therapies.

immunology↗

bioRxiv2021

CD47 cross-dressing by extracellular vesicles expressing CD47 inhibits phagocytosis without transmitting cell death signals

Transgenic CD47 overexpression is an encouraging approach to ameliorating xenograft rejection and alloresponses to pluripotent stem cells, and the efficacy correlates with the level of CD47 expression. However, CD47, upon ligation, also transmits signals leading to cell dysfunction or death, raising a concern that overexpressing CD47 could be harmful. Here, we unveiled an alternative source of cell surface CD47. We showed that extracellular vesicles (EVs), including exosomes (Exos), released from normal or tumor cells overexpressing CD47 (transgenic or native) can induce efficient CD47 cross-dressing on pig or human cells. Like the autogenous CD47, CD47 cross-dressed on cell surfaces is capable of interacting with SIRP to inhibit phagocytosis. However, ligation of the autogenous, but not cross-dressed, CD47 induced cell death. Thus, CD47 cross-dressing provides an alternative source of cell surface CD47 that may elicit its anti-phagocytic function without transmitting harmful signals to the cells. CD47 cross-dressing also suggests a previously unidentified mechanism for tumor-induced immunosuppression. Our findings should help to further optimize the CD47 transgenic approach that may improve outcomes by minimizing the harmful effects of CD47 overexpression.

immunology↗

bioRxiv2021

m6A-mediated Cell-cell Communication Controls Planarian Regeneration

Regeneration is the regrowth of damaged tissues or organs, a vital mechanism responding to damages from primitive organisms to higher mammals. Planarian possesses active whole-body regenerative capability owning to its vast reservoir of adult stem cells, neoblasts, thus provides an ideal model to delineate the underlying mechanisms for regeneration. N6-methyladenosine (m6A) regulates stem cell renewal and differentiation. However, how m6A controls regeneration at whole-organism level remains largely unknown. Here, we demonstrate that the depletion of m6A methyltransferase regulatory subunit wtap abolishes planarian regeneration, through regulating cell-cell communication and cell cycle. scRNA-Seq analysis unveils that the wtap knockdown induces a unique type of neural progenitor-like cells (NP-like cells), characterized by specific expression of the cell-cell communication ligand grn. Intriguingly, the depletion of m6A-modified transcripts grn/cdk9 (or cdk7) axis rescues the defective regeneration of planarian without wtap. Overall, our study reveals an indispensable role of m6A-dependent cell-cell communication essential for whole-organism regeneration.

molecular biology↗

bioRxiv2021

Comprehensive analysis of RNA-seq and whole genome sequencing data reveals no evidence for SARS-CoV-2 integrating into host genome

SARS-CoV-2, as the causation of severe epidemic of COVID-19, is one kind of positive single-stranded RNA virus with high transmissibility. However, whether or not SARS-CoV-2 can integrate into host genome needs thorough investigation. Here, we performed both RNA sequencing (RNA-seq) and whole genome sequencing on SARS-CoV-2 infected human and monkey cells, and investigated the presence of host-virus chimeric events. Through RNA-seq, we did detect the chimeric host-virus reads in the infected cells. But further analysis using mixed libraries of infected cells and uninfected zebrafish embryos demonstrated that these reads are falsely generated during library construction. In support, whole genome sequencing also didnt identify the existence of chimeric reads in their corresponding regions. Therefore, the evidence for SARS-CoV-2s integration into host genome is lacking. One-Sentence SummarySARS-CoV-2 does not integrate into host genome through whole genome sequencing.

genomics↗