Biology subjects

WANG, C.

Publications and source records attributed to WANG, C..

5 recordsLinked to original sources

bioRxiv2022

AnkG-Neurofascin complex structure reveals binding mechanisms required for integrity of the AIS

The axon initial segment (AIS) has characteristically clustering of voltage-gated sodium channels (Nav), cell adhesion molecule Neurofascin (Nfasc), and neuronal scaffold protein Ankyrin-G (AnkG) in neurons, which facilitate generation of action potential and maintenance of axonal polarity. However, the mechanisms underlying AIS assembly and maintenance remain poorly understood. Here we report the high-resolution crystal structure of the AnkG in complex with a fragment from Nfasc cytoplasmic tail that shows, in conjunction with binding affinity assays, the molecular basis of AnkG-Nfasc binding. We confirm AnkG interacts with the FIGQY motif in Nfasc, and identify another region required for their high affinity binding. Structural analysis revealed that ANK repeats form four hydrophobic or hydrophilic layers in the AnkG inner groove that coordinate interactions with Nfasc. Moreover, disruption of the AnkG-Nfasc complex abolishes Nfasc enrichment at the AIS in hippocampal neurons. Finally, structural and biochemical analysis indicated that L1 syndrome-associated mutations in L1CAM compromise binding with ankyrins. These results define the mechanisms underlying AnkG-Nfasc complex formation and show that AnkG-dependent clustering of Nfasc is required for AIS integrity.

biochemistry↗

bioRxiv2022

Spatial exploration of immune cell heterogeneity in skin functional scar-less wound regeneration model at single-cell resolution

Inevitable skin scarring devoid of dermal appendages bring about unfavorable effects on both aesthetic and physiological functions. Here we offered an available method for large-area wound regeneration using biodegradable Aligned extracellular matrix (ECM) scaffold. Accelerating wound coverage and enhanced hair follicle (HF) neogenesis were observed with the implantation of biomaterials. Multimodal analysis during wound regeneration provides a unique lens through which we can explore the foreign body responses (FBR) around biomaterials. First, we identified cell heterogeneity in responses to ECM scaffolds using single-cell RNA sequencing. Next the spatial anchor highlighted preferential recruitment of T cells around biomaterials colocalized with hair follicle precursor cells. Reconstruction of signaling pathways suggested the pro-regenerative effect of the adaptive immune systems on HF neogenesis. Immunodeficient mice lacking mature T lymphocytes lost the ability to activate papillary fibroblast as well as stimulate HF regeneration, validating the potential therapeutic effect of the adaptive immune system activated by biomaterials. In conclusion, this study provided the further understanding of the FBR and facilitate the design of immunoregulatory biomaterials for biomedical application in the future.

immunology↗

bioRxiv2021

Genome-wide screen identifies curli amyloid fibril as a bacterial component promoting host neurodegeneration

Growing evidence indicate that gut microbiota play a critical role in regulating the progression of neurodegenerative diseases, such as Parkinsons disease (PD). The molecular mechanism underlying such microbe-host interaction is unclear. In this study, by feeding C. elegans expressing human -syn with E. coli knockout mutants, we conducted a genome-wide screen to identify bacterial genes that promote host neurodegeneration. The screen yielded 38 genes that fall into several genetic pathways, including curli formation, lipopolysaccharide assembly, adenosylcobalamin biosynthesis among others. We then focused on the curli amyloid fibril and found that genetically deleting or pharmacologically inhibiting the curli major subunit CsgA in E. coli reduced -syn-induced neuronal death, restored mitochondrial health, and improved neuronal functions. CsgA secreted by the bacteria colocalized with -syn inside neurons and promoted -syn aggregation through cross-seeding. Similarly, curli also promoted neurodegeneration in C. elegans models of AD, ALS, and HD and in human neuroblastoma cells.

neuroscience↗

bioRxiv2020

Si-C: method to infer biologically valid super-resolution intact genome structure from single-cell Hi-C data

There is a strong demand for the methods that can efficiently reconstruct biologically valid super-resolution intact genome 3D structures from sparse and noise single-cell Hi-C data. Here, we developed Single-Cell Chromosome Conformation Calculator (Si-C) within the Bayesian theory framework and applied this approach to reconstruct intact genome 3D structures from the single-cell Hi-C data of eight G1-phase haploid mouse ES cells. The inferred 100-kb and 10-kb structures consistently reproduce the known conserved features of chromatin organization revealed by independent imaging experiments. The analysis of the 10-kb resolution 3D structures revealed cell-to-cell varying domain structures in individual cells and hyperfine structures in domains, such as loops. An average of 0.2 contact reads per divided bin is sufficient for Si-C to obtain reliable structures. The valid super-resolution structures constructed by Si-C demonstrates the potential for visualizing and investigating interactions between all chromatin loci at genome scale in individual cells.

bioinformatics↗

bioRxiv2020

Simultaneously monitoring aquatic and terrestrial biodiversity using riverine water eDNA: seasonal variation of monitoring effectiveness

Environmental DNA (eDNA) metabarcoding for biodiversity monitoring is a critical technical advance. Both aquatic and terrestrial biodiversity information can be detected in riverine water eDNA. However, it remains unverified whether riverine water eDNA can be used to simultaneously monitor aquatic and terrestrial biodiversity. Our specific objective was to assess the effectiveness of monitoring aquatic and riparian biodiversity using riverine water eDNA. We proposed that the monitoring effectiveness (the proportion of aquatic and terrestrial biodiversity information detected by riverine water eDNA samples) could be approximated by the transportation effectiveness of land-to-river and upstream-to-downstream biodiversity information flow. We conducted a case study in a watershed on the Qinghai-Tibet Plateau and estimated the effectiveness of using riverine water eDNA to monitor aquatic and riparian biodiversity based on comparing the operational taxonomic units (OTUs) and species assemblages of three taxonomic communities detected in riverine water eDNA samples and riparian soil eDNA samples in spring, summer, and autumn. The aquatic and riparian biodiversity of a watershed on the Qinghai-Tibet Plateau could be simultaneously effectively monitored using riverine water eDNA on summer or autumn rainy days. Monitoring bacterial communities was more efficient than monitoring eukaryotic communities. On summer rainy days, 43%-76% of riparian species could be detected in water eDNA samples, 92%-99% of upstream species could be detected in a 1-km downstream eDNA sample, and more than 50% of dead bioinformation (i.e., the bioinformation labeling the biological material without life activity and fertility) could be monitored 4-6 km downstream for eukaryotes and 13-19 km for bacteria. We encourage more studies on the monitoring effectiveness for each taxonomic community in other watersheds with different environmental conditions. We believe that in future ecological research, conservation and management, we could efficiently monitor and assess the aquatic and terrestrial biodiversity by simply using riverine water eDNA samples.

ecology↗