Biology subjects

Li, j.

Publications and source records attributed to Li, j..

3 recordsLinked to original sources

bioRxiv2025

Unheralded high MHC Class II polymorphism in the abundant Atlantic herring resolved by long-read sequencing

Major Histocompatibility Complex (MHC) genes are the most polymorphic in vertebrate genomes due to their important function of presenting a diversity of peptides from pathogens to initiate an adaptive immune response. Here, we have characterized MHC class II genes and explored their polymorphism and evolution in one of the most abundant vertebrates in the world, Atlantic herring (Clupea harengus). The vast population size and schooling behavior make Atlantic herring an attractive target for pathogens. Hence, we hypothesized that it would maintain exceptionally high MHC polymorphism. We used PacBio HiFi long-read whole genome sequencing data of 14 individuals from three different geographic regions in the Atlantic Ocean and Baltic Sea. The analysis identified nine MHC class II loci distributed across four chromosomes. We found two distinct lineages of class II genes, a highly polymorphic one denoted DA and a non-polymorphic DB lineage, arranged as alpha-beta gene pairs (DAA-DAB or DBA-DBB). The DA genes showed extremely high nucleotide diversity in exon 2, strong signatures of positive selection (dN/dS >> 1) as well as copy number variation. Structure prediction revealed that all highly polymorphic amino acid residues occurred in the predicted peptide binding cleft. Two of the most polymorphic loci showed distinct allelic groupings (supertypes), with high sequence similarity within supertypes and high sequence divergence between supertypes. Most of the haplotypes had genes from different supertypes, thus maintaining diverse class II repertoire in a single individual. There was also a highly significant nonrandom association of DAA and DAB alleles within supertypes, strongly suggesting coevolution of DAA and DAB alleles forming the peptide binding domain. This study reveals that the herring MHC class II genes are among the most, if not the most, polymorphic so far described in vertebrates. Their exceptional polymorphism surpasses that of human due to a larger gene repertoire, copy number variation, and pronounced sequence divergence among alleles. This unheralded polymorphism is most likely explained by the combined effects of the vast population size, minimizing genetic drift, and strong pathogen-driven balancing selection.

immunology↗

bioRxiv2023

TFvelo: gene regulation inspired RNA velocity estimation

RNA velocity is closely related with cell fate and is an important indicator for the prediction of cell states with elegant physical explanation derived from single-cell RNA-seq data. Most existing RNA velocity models aim to extract dynamics from the phase delay between unspliced and spliced mRNA for each individual gene. However, unspliced/spliced mRNA abundance may not provide sufficient signal for dynamic modeling, leading to poor fit in phase portraits. Motivated by the idea that RNA velocity could be driven by the transcriptional regulation, we propose TFvelo, which expands RNA velocity concept to various single-cell datasets without relying on splicing information, by introducing gene regulatory information. Our experiments on synthetic data and multiple scRNA-Seq datasets show that TFvelo can accurately fit genes dynamics on phase portraits, and effectively infer cell pseudo-time and trajectory from RNA abundance data. TFvelo opens a novel, robust and accurate avenue for modeling RNA velocity for single cell data.

bioinformatics↗

bioRxiv2020

Allergen specific Treg upregulated by lung-stage schistosome infection alleviates allergic airway inflammation via inhibiting IgE secretion

Schistosome infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist especially regarding the timing of helminth infection and the underlying mechanisms. Moreover, most previous studies focused on understanding the preventive effect of schistosome infection on asthma (infection before allergen sensitization), while its therapeutic effects (infection after allergen sensitization) were rarely investigated. In this study, we investigated the therapeutic effects of schistosome infection on AAI using a mouse model of OVA induced asthma. To explore how the timing of schistosome infection influences its therapeutic effect, the mice were percutaneously infected with cercaria of Schistosoma japonicum at either 1 day before OVA induced asthma attack (infection at lung-stage during AAI) or 14 days before OVA induced asthma attack (infection at post lung-stage during AAI). We found that lung-stage schistosome infection significantly ameliorated OVA-induced AAI, whereas post lung-stage infection showed no therapeutic effect. Mechanistically, the lung-stage schistosome infection significantly upregulated the frequency of Treg, especially OVA specific Treg, in lung tissue, which negatively correlated with the level of OVA specific IgE. Depletion of Treg in vivo counteracted the therapeutic effect. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage schistosome infection during AAI shaped the microenvironment to favor Treg induction. In conclusion, our data showed that lung-stage schistosome infection could relieve OVA induced asthma in a mouse model. The therapeutic effect was mediated by the upregulated OVA specific Treg which suppressed IgE production and Th2 cytokine secretion. Our results may facilitate the discovery of a new therapy for AAI. Author SummaryAsthma is an increasingly common disease especially in industrialized countries, which is still lack of an optimal therapy. The protective effect of schistosome infection against allergic asthma has been shown in previous studies, which represents a promising candidate immune intervention approach. However, controversial findings exist especially regarding the timing of helminth infection and the underlying mechanisms. In this study, we demonstrate that lung-stage schistosome infection could upregulate the frequency of allergen specific Treg, which significantly alleviated OVA induced allergic airway inflammation via inhibiting the production of IgE and Th2 cytokines. Our results proved the therapeutic effect of schistosome infection on allergic asthma. Moreover, we highlighted that lung-stage infection is essential for inducing allergen specific regulatory T cells in lung, which is the key mediator of the observed therapeutic effect. These findings shed new light on exploiting helminths or their derivatives to treat asthma and other allergic diseases.

immunology↗