BMC Biology最新文献

Background: The genetic basis of host resistance to viral infections is generally shaped by complex interactions between host genetic variations affecting antiviral immunity and the rapid evolutionary adaptability of viruses. In this study, we investigated two isogenic rainbow trout lines exhibiting extreme resistance or susceptibility to the rhabdovirus VHSV. We compared transcriptomes of the pronephros - a major lymphoid organ in fish - at steady state and following VHSV infection. By integrating bulk tissue RNA-seq with single-cell RNA-seq, we mapped the divergent transcriptomic responses of resistant and susceptible fish to specific immune cell types.

Results: At steady state, differences in antiviral pathways were minimal. However, VHSV triggered markedly distinct transcriptomic shifts between the lines. Both resistant and susceptible fish exhibited a broad transcriptional response enriched in core type I interferon (IFN) pathway genes. However, line-specific responses were enriched in genes induced by infection independently of type I IFN. In resistant fish, lymphocyte responses included type I IFN pathway, numerous transcription factors, and various cytokine receptors. In contrast, lymphocyte responses in susceptible fish involved only a limited set of type I IFN-induced genes. Monocytic cell responses also diverged: susceptible fish upregulated IFN-induced genes, while resistant fish showed increased expression of proinflammatory genes.

Conclusions: This study reveals the contribution of the core set of interferon-stimulated genes conserved across vertebrates to the response of different immune cells and the response of other genes in resistant and susceptible fish. It provides a comprehensive basis for evolutionary studies of resistance to viruses in vertebrates.

Background: In the in vitro expansion of mesenchymal stem cells (MSCs), replicative or stress-induced senescence poses a significant challenge, leading to the loss of their cellular properties and therapeutic functions. Currently, there is a lack of efficient strategies to address this issue.

Results: Here we presented a novel approach to combat cellular senescence and promote cell proliferation by coculturing human MSCs with human peripheral blood lymphocytes (PBLs). In a heterogeneous population of MSCs comprising both aged and nonaged cells, PBL effector cells, rather than their cytokines, exhibited a dual role. They selectively induced apoptosis in aged cells by facilitating p53 SUMOylation and activating the p53-dependent mitochondrial pathway, while simultaneously safeguarding younger cells against senescence and promoting cell proliferation by activating Serpinb2/NF-κB signaling. This resulted in a decrease in aged MSCs and an enrichment of rejuvenated MSCs. This process effectively reversed the senescence phenotype, leading to the remodeling of stemness characteristics and the enhancement of functionality within the MSC population. Furthermore, MSCs rejuvenated by PBLs presented an enhanced therapeutic efficacy and a favorable safety profile.

Conclusions: PBLs rejuvenate MSCs by promptly removing aged cells and enhancing the stemness and proliferative capacity of nonaged cells. This work provides an ideal method for obtaining substantial MSCs while meeting the quality requirements for stem cell therapy.

Background: Recent studies focus on the genetic and physiological characteristics of the plains Han, plateau Han, and Tibetan populations. However, systematic studies on the differences in metabolic and microbial communities in high-altitude environments remain limited.

Results: This study profiled metabolomes and microbiomes in plain Han, plateau Han, and Tibetan populations. Differential analysis revealed 30 metabolites and notable alterations in microbial community composition between plain Han and plateau Han. Prevotella, Streptococcus, and Ruminococcus, mainly participating in purine metabolism, were enriched in the plateau Han population. Bacteroidota and Firmicutes were the primary differential bacterial phyla indicating adaptive alternatives, particularly in steroid metabolism. Thirty-four distinct metabolites were identified between plateau Han and Tibetan individuals, including significant lipids such as ceramide, triglycerides (TG), and phosphatidylethanolamine (PE). These lipids and metabolites were integrally involved in energy metabolism and inflammatory pathways, highlighting the importance of high-altitude environments for metabolic health.

Conclusions: This study identified significant associations between metabolic, lipid, and microbial differences and altitude-induced physiological variation, illustrating population adaptations to extreme environments. Our systematic comparative analysis improves our understanding of high-altitude adaptability, underlining the importance of integrating metabolic and microbiological analyses and facilitating future research on associated disorders.

Background: Echinoid larvae are known to display food-induced phenotypic plasticity, where larvae alter their morphology and physiology to reflect available food levels. The aim of this study was to describe the induction and reversal of morphological and physiological plasticity through the entirety of larval development of the sand dollar Dendraster excentricus.

Results: When larvae fed a low algal ration were switched to high food conditions at 10-, 20-, and 30-day post-fertilization, we observed rapid induction of the high-fed phenotype as indicated by decreases in postoral arm length (POAL) as well as changes in assimilation and growth efficiencies. Switched larvae required more time to develop, but due to physiological changes in assimilation efficiency, they expended the same total amount of energy to achieve metamorphic competence as constantly high-fed larvae. These morphological results were also confirmed by tracking individual larvae in separate experiments. When larvae were switched from high to low food conditions, short-armed larvae rapidly experienced significant increases in POAL.

Conclusions: These results establish that plasticity responses in echinoid larvae are both reversible and inducible throughout larval development and result in significant adaptive benefits in terms of energy use. Our single larval experiments facilitate future analyses that can explore the genetic and molecular underpinnings of phenotypic plasticity.

Background: Sub-Antarctic marine ecosystems are highly vulnerable to climate change, with rising ocean temperatures threatening key benthic species. Abatus cordatus, an endemic sea urchin of the Kerguelen Islands with limited dispersal capacity, has been hypothesised to possess a narrow thermal niche, which would render it particularly susceptible to environmental shifts. However, microbiome-mediated acclimation may provide a potential mechanism of resilience to ocean warming. To test these hypotheses, this study evaluates host survival and gut microbiome responses of A. cordatus to medium-term seawater warming under near-future temperature scenarios using 16S rRNA gene sequencing to compare these changes with those observed in sediment microbiomes.

Results: Host mortality remained relatively low across all temperatures, showing no association with warming intensity and thereby suggesting thermal tolerance. While gut microbiome alpha-diversity remained stable, its composition shifted and variability increased with experiment duration and temperature, leading to greater inter-individual divergence and a decline in both the richness and abundance of core taxa. In contrast, sediment microbiomes remained more stable, exhibiting more deterministic assembly and increased core stability over time. At the taxonomic level, specific gut bacterial ASVs showed temperature-dependent abundance shifts, with greater flexibility at moderate thermal stress. Notably, the depleted and enriched ASVs were affiliated to known sulphate-reducing and fermentative taxa, respectively, suggesting a possible functional shift.

Conclusions: Overall, our findings suggest that A. cordatus can tolerate medium-term warming, with gut microbiome plasticity representing a potential mechanism supporting host resilience.

Background: Bacteriophages and bacteria frequently occupy the same ecological niches, driving complex and dynamic host-virus interactions. In Pseudomonas aeruginosa, phages from the Migulavirinae subfamily, tail fibre proteins (TFPs) are crucial to host recognition. These proteins, located within the phage tail structure, are subject to frequent recombination and may play a key role in shaping host range. This study investigates the molecular basis of host specificity in Litunavirus and Luzseptimavirus phages, focusing on the structure and variation of their TFPs.

Results: Host spectrum analysis divided phages into three categories; however, contrary to expectations, no direct correlation was found between TFP recombination history and host range, most likely because subsequent single amino acid changes in the pyocin knob regions, critical for adsorption, altered the host spectrum after the recombination event. Notably, phages sharing highly similar pyocin knob 2 domain architectures displayed identical host spectra, suggesting a strong link between this region and host specificity. Despite high sequence variability, all TFPs adopted a conserved trimeric fold with five regions: N-terminal, GrpE-like, GDSL-like with a carbohydrate-binding module, pyocin knob, and C-terminal. Structural similarities to bacterial PilA and pyocins were noted. Variation in the pyocin knob region, especially substitutions involving polar residues, was partially correlated with host range, likely via hydrogen bonding with the O-antigen. The GrpE-like domain resembled type IV pili, suggesting a role in reversible attachment, while the GDSL-like domain may support enzymatic processing of the O-antigen.

Conclusions: Our findings support a multi-step adsorption mechanism of Migulavirinae phages, initiated by random encounters with the bacterial surface, followed by specific, stable interactions between the pyocin knob region and the bacterial lipopolysaccharide (LPS) O-antigen. Final stabilization involves additional interactions with the LPS core region. While the GrpE-like domain may contribute to transient stabilization near the surface, its structural similarity to PilA suggests a possible evolutionary convergence rather than a direct pilus-binding function. Despite high sequence variability, TFPs maintain conserved structural features, allowing for modular adaptations that precisely adjust host specificity. Importantly, the lack of a direct link between TFP recombination and host range suggests that factors beyond recombination influence phage host specificity.

Background: Despite only limited sampling, the holoparasitic plant family Balanophoraceae harbors extreme mito-genome diversity and also has exceptionally divergent plastomes. We therefore sequenced the mitochondrial, plastid, and nuclear genomes of Balanophora yakushimensis and its transcriptome.

Results: At 1.1 Mb, the B. yakushimensis mitogenome is one of the largest known mitogenomes. Driving this expansion and generating the most repeat-rich mitogenome in land plants are many large (up to 200 kb) duplications and a massive proliferation of short, AT-rich repeated sequences. The repeat proliferation, in conjunction with a highly elevated and unusually AT-biased mutation rate, has produced what is by far the most AT-rich land-plant mito-genome. These invasive repeats also created giant introns, unprecedented in size for organelles, and greatly expanded all rDNA exons. We discovered a record-low, for all genomes, transition/transversion ratio (0.12) in B. yakushimensis mtDNA and documented a 26-fold range in this ratio across angiosperm mitogenomes. The B. yakushimensis nuclear genome has lost exceptionally many genes that function in organellar DNA recombination, repair, and replication (RRR). We discuss ways in which these losses-and other genetic alterations as well as non-genetic ones-may or may not be related to the unusual features of both its mitochondrial and plastid genomes.

Conclusions: The mitogenome of B. yakushimensis possesses many exceptional, indeed record-setting properties. The unprecedented loss of nuclear genes for organellar DNA RRR may explain some of these unusual features. These findings expand the boundaries of mitogenome deviancy and raise outstanding questions about the forces driving such extravagantly diversifying evolution.

Background: Insects have evolved various antipredator defenses, some of which produce copious chemicals when threatened, such as ants, beetles, butterflies, moths, stick insects, and true bugs. The true bugs (Hemiptera: Heteroptera) are known for their foul odor, which comprises over 45,000 species of biologically and economically important insects. One key element to the success of heteropterans is the evolution of specialized defensive glands, specifically the metathoracic scent gland in adults and the dorsal abdominal scent glands in nymphs, a hallmark synapomorphy for the clade. Within Pentatomomorpha, the scent gland peritreme exhibits remarkable morphological diversity, yet its evolutionary origins and drivers remain poorly understood due to sparse fossil evidence of these delicate structures.

Results: We report a series of Mesozoic fossils with well-preserved scent gland anatomy, including the earliest evidence from the Jurassic (165 million years ago), revealing an ancestral auricle-type morphology. Ancestral-state reconstruction across 40 extant and fossil taxa confirms the auricle as the plesiomorphic condition for Pentatomomorpha. Fossil evidence demonstrates phenotypic diversification by the Early Cretaceous (~ 125 Ma), with many peritreme types (auricle, spout, groove) emerging by the mid-Cretaceous. Developmental analyses of extant taxa show no pre-adult differentiation, indicating rapid peritreme formation during the final molt.

Conclusions: The scent gland peritreme evolved as a rapidly developing from a simple underdeveloped to auricle to five well-developed basic derived types in early Pentatomomorpha. Its subsequent diversification into specialized forms coincided with mid-Mesozoic habitat shifts and predator pressures, particularly during angiosperm proliferation. Convergent morphologies across lineages reflect shared ecological constraints and developmental plasticity.

Background: Large-scale Y-chromosome genetic resources provide critical insights into human evolutionary history. However, the limited high-density Y-chromosomal data from ethnolinguistically diverse Chinese populations hinder the reconstruction of fine-scale population stratification and the exploration of its complex influencing factors.

Objectives: We report microarray-based high-density Y-SNP data from 5311 unrelated males in the pilot phase of the 10K Chinese People Genomic Diversity Project (10K_CPGDP) and merge it with spatiotemporally high-coverage reference data from both ancient and modern individuals from public sources and the Huaxi Biobank dataset.

Results: We identified clear north-south and west-east genetic substructures among Chinese populations, reflecting distinct regional genetic origins and migration patterns. We illuminated how multiple cultural and demographic factors, including subsistence strategies, language barriers, and geographic isolation, have shaped the Chinese paternal population dynamics via genetic diversity analysis coupled with phylogenetic and phylogeographic analyses. Paternal genetic diversity followed complex patterns, with a haplogroup frequency spectrum and a variation-based phylogenetic tree indicating that more than 95% of paternal lineages belong to haplogroups O, C, N, D, and Q. The phylogeographic analysis revealed distinct regional distributions of haplogroups linked to subsistence strategies and ancestral population dispersal. The predominance of Neolithic farmer-related lineages suggested that the spread of ancestral agricultural populations promotes population differentiation between ancient northern and southern East Asians. We observed significant lineage sharing between Han Chinese and ethnic minority groups, with the northwestern paternal gene pool contributing lineages associated with farming and herding. Spatial autocorrelation and principal component analyses revealed genetic connections between the Han Chinese and ethnic minorities, highlighting paternal population substructures shaped by complex admixture and migration patterns that align with geographical and linguistic divisions.

Conclusions: These findings support the influence of the farming-language dispersal hypothesis on Chinese paternal lineage formation and underscore the role of geographic and linguistic isolation in shaping the genetic landscape. This study demonstrates the unique value of large-scale Y-chromosome data in uncovering human evolutionary complexity.

Background: The presence and function of microtubules within the synaptic bouton has long been under investigation. In recent years, evidence has accumulated that connects the synaptic vesicle cluster to the local dynamics of microtubule ends. Nonetheless, one question remains open, namely whether the vesicles influence the availability of tubulin within the synaptic compartment.

Results: An analysis of previously published live imaging experiments indicates that tubulin is strongly enriched in the synaptic vesicle cluster. To analyze the vesicle-tubulin interaction directly, we isolated vesicles from the mouse brain and imaged them together with fluorescent tubulin in vitro. We found that soluble tubulin is collected by synaptic vesicles in physiological buffers, resulting in the formation of tubulin-rich regions (TRRs) on the respective vesicle clusters.

Conclusions: We conclude that the synaptic vesicle cluster is indeed able to recruit soluble tubulin.