Biology subjects

Ke, F.

Publications and source records attributed to Ke, F..

11 recordsLinked to original sources

bioRxiv2026

Understanding highland adaptation of Apis cerana through repeated while independent colonization

Understanding the genetic basis of polygenic adaptation is challenging. Populations that undergo parallel evolution serve as experimental replications enabling the study of molecular mechanism. Apis cerana is widely-distributed in Asia and has repeatedly colonized the Qinghai-Tibet Plateau. The highland populations are derived from lowland colonies while showed not admixture with each other, representing independent events of colonization. We investigated resequencing genomes of five populations to study the genetic basis of highland adaptation in A. cerana. Using two complementary methods, we isolated genes with adaptive signals in each lineage. Although large proportion of adaptive loci are unique to each population, most potentially adaptive polymorphism shared with genetic variation in lowland populations, consistent with widespread signals of soft selection sweeps. Whereas parallelism was low at the level of adaptive loci, it was greater for functional pathways and greatest for phenotypes. Further enrichment analysis found the shared adaptive loci were overrepresented in pathways related to the development of sensory system and body morphogenesis. These highly connected pathways and loci could buffer different genetic paths and maintain developmental stability. Adaptive signals in the development-related loci suggest stabilizing selection further drive phenotypic convergence under similar stress. However, lineage-specific loci and pathways facilitated adaptive divergence in each lineage within the broadly similar highland environment. Our results demonstrate the genetic redundancy of highland adaptation and lineage-specific evolution via independent colonization in A. cerana. This underscores that predicting a populations adaptive potential requires understanding its full adaptive architecture within the ecological context--including abiotic and biotic interactions.

evolutionary biology↗

bioRxiv2025

Albumin-STING Nanocomplex Reprograms HSPCs to Antitumor Neutrophils with Enhanced MHC I Antigen Presentation for Cancer Immunotherapy

Tumor-associated immunosuppressive neutrophils, termed myeloid-derived suppressor cells (MDSCs), compromise cancer immunotherapy. They can be pathologically programmed as early the hematopoietic stem and progenitor cell (HSPC) stage by suppressing interferon signaling. Reprogramming HSPCs toward antitumor neutrophils through the stimulator of interferon genes (STING) activation offers a promising therapeutic strategy. Here, we demonstrate that an albumin-STING nanoagonist (Nano ZSA-51D) reprograms HSPCs to generate antitumor neutrophils, enhancing MHC I-mediated CD8 T cell immunity. Nano ZSA-51D activates STING-interferon signaling in HSPCs, promoting their expansion and differentiation toward granulocyte-monocyte progenitors via STING-NF-{kappa}B-IL-6 signaling. It further reprograms neutrophils into CD14ICAM-1+ subset through STING-NF-{kappa}B-TNF- signaling, enhancing tumor infiltration. These neutrophils upregulate interferon signaling and MHC I antigen presentation, boosting tumor-specific CD8 T cell responses. Adoptive transfer of Nano ZSA-51D-reprogrammed neutrophils with -PD1 therapy achieves complete colon tumor remission. Our findings provide a novel strategy to reprogram HSPCs toward antitumor neutrophils and highlight the potential of early interventions at HSPC stage to rewire neutrophil fate for cancer immunotherapy.

immunology↗

bioRxiv2025

Characterization of bronchovascular-bundle mesenchymal stromal cells regulating antibody-secreting cell niche in rejecting lung allografts

A transplanted lung offers a permissive milieu for local adaptive immune cell responses. Here, we characterize a transcriptionally and anatomically distinct adult lung-resident mesenchymal stromal population (MSC) that supports a pro-survival niche for antibody-secreting cells in rejecting lung allografts through a novel IL-6 trans-signaling/CXCL12 axis. By using a mouse orthotopic lung transplant model and Blimp1EYFP recipients, we identify spatial localization of antibody-secreting cells (ASCs) and terminally differentiated plasma cells (PCs) along the bronchovascular bundles (BVBs). A previously described Foxf1+Gli1+Itga8- subset of collagen- expressing MSCs, which forms a 3-dimensional network along the bronchovascular bundles (BVB-MSCs), was found to be the major source of the PC survival factors CXCL12 and IL-6. Cxcl12iCre/ERT2Rosa26tdTomatomice utilized as donors, validated the expansion of this population in a rejecting graft and their intimate association with ASCs. CXCL12 expression was increased in murine allografts and in Foxf1+ mesenchymal cells (MCs) isolated from human CLAD patients. IL-6 trans-signaling/STAT3 signaling axis was shown to upregulate CXCL12 secretion in human MCs, and Olamkicept-mediated neutralization of IL-6 trans-signaling in murine RAS attenuates CXCL12 expression, intra-graft ASC population, and fibrogenesis. Our findings represent the first delineation of specialized CXCL12-expressing mesenchymal stromal cells in adult lungs and the contribution of IL-6 trans-signaling driven CXCL12 expression to sustaining intra-graft ASC niches and allograft fibrogenesis. One Sentence SummaryWe characterize CXCL12-expressing mesenchymal cells and their role in a pro-survival niche for antibody-secreting cells in rejecting lung allografts.

pathology↗

bioRxiv2024

Contribution of GC content to differentiated region formation along a speciation continuum

Genome architecture can interact with evolutionary processes and be involved in the formation of differentiated regions potentially containing adaptation and speciation loci. Regions of low GC content can be linked to low mutation and recombination rates. These effects on the formation of heterozygous differentiation landscapes have not been investigated. Here, we explored mutation accumulation and group divergence along a speciation continuum using 499 genomes of Apis cerana, with a widely distributed Central group diverged with its peripheral groups at both population genetic and phylogenetic timescales. We found that the differentiated regions had generally lower recombination and GC content than the rest of the genome, with lower-than-average divergence (dxy) initially to higher-than-average ones at deeper timescale. Most rare alleles ([~]80%) are AT-biased that derived from GC, resulting in lower AT-biased mutations in low-GC regions. Multiple regression analysis further shows that reduced mutation and recombination rates are associated with decreased diversity, particularly in regions with low GC content. Moreover, in all A. cerana groups, higher mutation load and less efficient selection in low-GC regions compared with high-GC regions suggest that restricted recombination is important in mutation accumulation (e.g., AT-biased) and group divergence. This pattern explains the increased dxy in low-GC regions over evolutionary time. Finally, low-GC regions possess higher proportion of group-specific polymorphisms, which reconciliate discordance between mitochondrial and nuclear phylogenies in A. cerana. Our results highlight the contribution of genome architectures to the formation of differentiation landscapes along divergent groups, emphasizing caution regarding loci identified solely from differentiated regions. Significance StatementThis study shows the low nucleotide diversity in differentiated regions could be simply attributed to genome architectures (e.g., gBGC, local recombination and mutation rates). Further studies should consider the effects of genome architecture on understanding the formation of heterozygous differentiation landscape along diverging groups and identification of adaptive loci.

evolutionary biology↗

bioRxiv2024

SARS-CoV-2 B Epitope-Guided Neoantigen NanoVaccines Enhance Tumor-Specific CD4/CD8 T Cell Immunity Through B Cell Antigen Presentation

Current neoantigen cancer vaccines activate T cell immunity through dendritic cell /macrophage-mediated antigen presentation. It is unclear whether incorporating B cell-mediated antigen presentation into current neoantigen vaccines could enhance CD4/CD8 T cell immunity to improve their anticancer efficacy. We developed a SARS-CoV-2 B cell epitope-guided neoantigen peptide/mRNA cancer nanovaccines (BSARSTNeoAgVax) to improve anticancer efficacy by enhancing tumor-specific CD4/CD8 T cell antitumor immunity through B cell-mediated antigen presentation. BSARSTNeoAgVax crosslinked with B cell receptor, promoted SARS-CoV-2 B cell-mediated antigen presentation to tumor-specific CD4 T cells, increased tumor-specific follicular/non-follicular CD4 T cells, and enhanced B cell-dependent tumor-specific CD8 T cell immunity. BSARSTNeoAgVax achieved superior efficacy in melanoma, pancreatic, and breast cancer models compared to the current neoantigen vaccines. Our study provides a universal platform, SARS-CoV-2 B epitope-guided neoantigen nanovaccines, to improve anticancer efficacy against various cancer types by enhancing CD4/CD8 T cell antitumor immunity through viral-specific B cell-mediated antigen presentation.

immunology↗

bioRxiv2023

Characterization of Z chromosomal inversion and lineage-specific sweeps reveal widespread local adaptation in Helicoverpa armigera

Efficient pest management requires comprehensive knowledge of its biology, ecology, and evolution, particularly adaptation that exacerbating pest damage. Helicoverpa armigera (Hubner) is a notorious pest that attacks more than 200 species, adapts to diverse environments, and has developed resistance to almost all applied insecticides. However, local adaptation of this species was less investigated. Here, we analyzed genomic variation of Helicoverpa armigera in China and Oceania to identify adaptative loci in different lineages. Despite intensive gene flow, two differentiated Z chromosomal lineages in Central China (i.e., northern and southern lineages) were formed by chromosome inversion and local adaptation. Based on population genomic analysis, we identified genes related to circadian clock (period, cycle, cyr2 and daywake), insulin secretion (IGF2BP2) and energy metabolism (SLC25A25, CCG7766, D11DS, TSTP and CPQ) were under selection in northern lineage. These genes may have contributed to its adaptation to high latitudes. In the southern lineage however, the Z chromosome inversion harboring alien alleles of two clock genes (period and cycle) and may have disrupted clock oscillator for adaptation. We further conducted selective sweep analysis in lineages from Northwestern China, Central China, and Oceania, and found several insecticide resistant genes that shared among different lineages were likely contributed by introgression. Nevertheless, many candidates, including a cadherin that involved in resistance to Bacillus thuringiensis protein in Oceanian populations, are lineage-specific. Our results highlight the importance of investigating local adaptation in effective pest control under globalization of agriculture.

evolutionary biology↗

bioRxiv2023

Genetic basis and evolution of structural color polymorphism in an Australian songbird

Island organisms often evolve phenotypes divergent from their mainland counterparts, providing a useful system for studying adaption under differential selection. Some island birds have melanic plumage differing from the color of mainland conspecifics, a trait proposed as an insular adaptation. In the white-winged fairywren (Malurus leucopterus), subspecies on two islands have a black nuptial plumage whereas the subspecies on the Australian mainland has a blue nuptial plumage. The black subspecies have a feather nanostructure that could produce a blue structural color, suggesting a blue ancestor. An earlier study proposed independent evolution of melanism on the islands based on the history of subspecies divergence. However, the genetic basis of melanism and the origin of color differentiation in this group are still unknown. Here, we used whole-genomes to investigate the genetic basis of melanism by comparing the blue and black M. leucopterus subspecies to identify highly divergent genomic regions. We identified a well-known pigmentation gene ASIP and four candidate genes that may contribute to feather nanostructure development. We also detected signatures of a selective sweep in genomic regions containing ASIP and SCUBE2 not in the black subspecies, as predicted by earlier work, but in the blue subspecies, which possesses many derived SNPs in these regions, suggesting that the mainland subspecies has re-evolved a blue plumage from a black ancestor. This re-evolution was likely driven by a pre-existing female preference. Our findings provide new insight into the evolution of plumage coloration in island versus continental populations, and, importantly, we identify candidate genes that likely play roles in the development and evolution of feather structural coloration.

evolutionary biology↗

bioRxiv2022

Nuclear proteins acquiring Germinal Center B cells are specifically suppressed by follicular regulatory T cells.

Follicular regulatory T cells (Tfrs) restrict development of autoantibodies and autoimmunity while supporting high-affinity foreign antigen-specific humoral response. However, whether Tfrs can directly repress germinal center (GC) B cells that acquire auto-antigens is unclear. Moreover, TCR specificity of Tfrs to self-antigens is not known. Our study suggests that nuclear proteins contain antigens specific to Tfrs. Targeting of these proteins to antigen-specific B cells triggers rapid accumulation of Tfrs with immunosuppressive characteristics. Tfrs then exert negative regulation of GC B cells with predominant inhibition of the nuclear protein-acquiring GC B cells, suggesting an important role of direct cognate Tfr-GC B cells interactions for the control of effector B cell response.

immunology↗

bioRxiv2018

B cells transiently exposed to antigen that return to quiescence respond to protein immunization similarly to naive B cells

Transient exposure of B cells to moderately multivalent antigens has been shown to lead to their activation and recruitment into T-dependent B cell response in the presence of T cell help. However, when T cell help is delayed, transiently activated B cells return to a naive-like state. While B cells that briefly encountered cognate antigen and then underwent inactivation are not tolerant, whether they may be hypo-or hyper-responsive to cognate antigen is not known. In this study we show that naive B cells and those previously exposed to antigen and then inactivated generate comparable germinal center and plasma cell responses after immunization with a wide range of antigen concentrations.

immunology↗

bioRxiv2018

B cell receptor crosslinking can augment T cell help-mediated germinal center B cell selection.

Selection of germinal center (GC) B cells with B cell receptors (BCR) possessing high affinity to foreign antigen (Ag) and their differentiation into antibody-secreting long-lived plasma cells is critical for potent long-term humoral immunity. Ag-dependent engagement of GC B cell BCR triggers Ag internalization and loading of antigenic peptides on MHCII molecules for presentation to follicular helper T cells (Tfh) and acquisition of T cell help. However, whether it also provides signals that are critical or synergistic with T cell help for GC B cell selection and differentiation in vivo is not known. Here we show that T cell help is sufficient to induce GC B cell expansion and plasmablast (PB) formation in the absence of recurrent BCR engagement with Ag. Ag-mediated BCR crosslinking on the other hand is not sufficient to promote GC B cell selection, but can synergize with T cell help to enhance the GC B cell and PB responses when T cell help is limiting.

immunology↗

bioRxiv2018

CCL3 promotes germinal center B cells sampling by follicular regulatory T cells and ensures optimal humoral response

Previous studies and our findings suggest upregulated expression of proinflammatory chemokines CCL3/4 in germinal center (GC) centrocytes. However, the role of CCL3/4 for centrocyte interactions with follicular T cells and regulation of humoral immunity is poorly understood. We found that CCL3 promotes chemotaxis of Tfr cells ex vivo. In vivo CCL3 is not required for Tfr cells recruitment of into the GC light zone. However, B cells-intrinsic production of CCL3 promotes their direct interactions and negative regulation by follicular regulatory T cells (Tfr) within GCs.

immunology↗