Biology subjects

Zhou, T.

Publications and source records attributed to Zhou, T..

At least 73 records · Page 4Linked to original sources

bioRxiv2025

Type 1 Regulatory T cells induced by intestinal epithelial cells respond to food antigen

As the first-line barrier against food antigens, the intestinal epitheliums role in establishing peripheral immune tolerance to food remains completely unknown. Additionally, the specific types of regulatory T cells induced to maintain food tolerance--along with their antigen specificity--are still unclear. Here we found small intestinal FOXP3-IL-10+ Tr1 cells, but not Treg cells, can respond to food antigens presented by intestinal epithelial cells (IECs) in an antigen-specific manner. Through immunopeptidome analysis of MHCII-presented peptides, we demonstrate that IECs can present food-derived antigens. Importantly, these IEC-presented food antigens are exclusively recognized by the TCR repertoire of small intestinal Tr1 cells, not Treg cells. Furthermore, we show that T cells recognizing IEC-presented food antigens specifically differentiate into Tr1 cells in the siLP. These findings establish two key insights: first, that maintaining food tolerance represents a physiological function of Tr1 cells, and second, that IECs play a central role in maintaining food tolerance. Our work thus provides mechanistic understanding of how the intestinal epithelium contributes to immune tolerance through its antigen presentation capacity and subsequent Tr1 cell induction.

immunology↗

bioRxiv2025

Human iPSC derived alveolar macrophages reveal macrophage subtype specific functions of itaconate in M. tuberculosis host defense

Mycobacterium tuberculosis (Mtb) must survive within multiple macrophage populations during infection, including alveolar macrophages (AM) and recruited inflammatory macrophages. In mice, itaconate, produced in macrophages by ACOD1 mediated decarboxylation of aconitate, has direct antimicrobial activity, modulates inflammatory cytokines, and is required for resistance to M. tuberculosis (Mtb) infection. The role of itaconate in human macrophages is less clear and whether itaconate mediates distinct effects in macrophage subtypes is unknown. Here, we investigated the role of itaconate in human iPSC-derived macrophages, either induced by GM-CSF to resemble alveolar macrophages (AM-Like cells), or treated with M-CSF to generate control macrophages (MCDM cells). Both types of human macrophages produce substantially less itaconate than mouse macrophages and AM-Ls produced 4-fold less itaconate than MCDMs. Surprisingly, ACOD1 deficient AM-L macrophages, but not MCDM macrophages, were permissive for Mtb growth. Moreover, itaconate functioned to dampen the Mtb induced inflammatory response in MCDMs, but not AM-L macrophages, affecting both the Type I IFN and TNF pathways. These results indicate that itaconate is involved in human macrophage responses to TB, with distinct roles in different macrophage subsets. These results also show that genetically tractable hiPSC-derived macrophages are a robust and versatile model to dissect cellular host pathogen interactions.

immunology↗

bioRxiv2025

An efficient artificial esterase with a dynamic conformation via conformational engineering

The catalytic turnover number (kcat) of current enzyme mimics and de novo designed enzymes is still orders of magnitude lower than that of natural enzymes, because mimicking the fast-dynamic feature of enzyme active centers remains a great challenge. Herein, we created a gold nanoparticle-based artificial esterase, Goldenzyme, by conformational engineering to reconstruct dynamic active centers resembling that of -chymotrypsin. NMR characterization shows that Goldenzyme possesses a fast-dynamic feature, about 6-fold faster than typical -helix. Therefore, Goldenzyme efficiently hydrolyzes p-nitrophenyl acetate with a net kcat of 6.37 s-1 per active center, more than 5-fold of that of -chymotrypsin (1.19 s-1), and Goldenzyme can even hydrolyze some non-activated esters that -chymotrypsin cannot. Our conformational engineering approach demonstrates the possibility of creating artificial enzymes that surpass natural ones.

biochemistry↗

bioRxiv2025

Mitochondrial calcium influx-driven bioenergetics in the dopaminergic system selectively enable drug reward

Drugs of abuse hijack the brains reward system, driving pathological dopamine surges that underlie compulsive behavior and addiction. However, directly targeting dopamine signaling for treatment risks disrupting natural reward processes. Here, we identify a bioenergetic mechanism that selectively promotes addiction-related dopamine release and behaviors. Opioids and methamphetamine, but not natural rewards, induce mitochondrial calcium (Ca2+) influx via the mitochondrial calcium uniporter (MCU) in dopaminergic terminals of the nucleus accumbens. Optogenetic stimulation reveals that this mitochondrial Ca2+ influx occurs exclusively during high-intensity dopaminergic neuronal activation. This Ca2+ influx drives rapid ATP production, compensating for energy deficits caused by neuronal hyperactivity and enabling sustained dopamine release. Genetic deletion or pharmacological inhibition of MCU in dopaminergic neurons selectively reduces drug-induced dopamine release and prevents addictive behaviors while sparing natural reward processing in mice. These findings uncover a distinct mitochondrial bioenergetic mechanism underlying drug reward and propose MCU as a promising therapeutic target for addiction treatment.

neuroscience↗

bioRxiv2025

A high-throughput immunopeptidome platform for MHC II alleles to characterize antigen-specific CD4 + T cells

CD4+ T cells play a pivotal role in adaptive immunity, recognizing peptide antigens presented by MHC II molecules during infections and tumor development. Identifying immunodominant MHC II epitopess is essential for understanding CD4+ T cell responses; however, current methods such as mass spectrometry, suffer from low sensitivity and throughput, while computational algorithms show variable accuracy. To overcome these challenges, we developed EliteMHCII, a high-throughput immunopeptidome profiling platform that identifies antigen-derived MHC II epitopes and measures peptide binding affinity across 24 globally common MHC II alleles. Using EliteMHCII, we assessed the immunodominant epitopes of the SARS-CoV-2 RBD protein. Validation in vaccinated individuals and humanized mouse models revealed a strong correlation between high-affinity peptides and robust CD4+ T cell responses, while low-affinity peptides failed to elicit responses. Therefore, our immunopeptidome profiling platform, EliteMHCII, serves as a rapid, high throughput, feasible platform for CD4+ T cell epitope discovery at a global populational level in the context of infectious diseases and cancer immunotherapy.

biochemistry↗

bioRxiv2025

VIProDesign: Viral Protein Panel Design for Highly Variable Viruses to Evaluate Immune Responses and Identify Broadly Neutralizing Antibodies

MotivationHighly mutable viruses continuously evolve, with some posing major pandemic risks. However, standardized neutralization assays and up-to-date viral panels are often lacking, limiting evaluation of immunogens and identification of broadly neutralizing antibodies. Closing these gaps is essential for guiding effective countermeasure development. ResultsIn this study, we present Viral Protein Panel Design (VIProDesign), a computational tool for designing viral protein panels that address the high sequence diversity of rapidly evolving viruses. VIProDesign uses the Partitioning Around Medoids (PAM) algorithm to select representative strains and applies the elbow-point method based on cumulative Shannon entropy to balance diversity and panel size. We used VIProDesign to generate optimized panels for Betacoronavirus, human immunodeficiency virus-1 (HIV-1), Influenza virus, Norovirus, and Lassa virus. The tool also supports customizable panel sizes, making it suitable for both resource-limited contexts and early-stage research. This flexible approach streamlines viral panel design across diverse pathogens. Although VIProDesign was originally developed for viral proteins, its underlying framework is broadly applicable to the selection of representative protein panels across diverse taxa, including bacterial species, toxins, and other biologically relevant protein families.

bioinformatics↗

bioRxiv2025

POPARI: Modeling multisample variation in spatial transcriptomics

Integrating spatially-resolved transcriptomics (SRT) across biological samples is essential for understanding dynamic changes in tissue architecture and cell-cell interactions in situ. While tools exist for multisample single-cell RNA-seq, methods tailored to multisample SRT remain limited. Here, we introduce PO_SCPLOWOPARIC_SCPLOW, a probabilistic graphical model for factor-based decomposition of multisample SRT that captures condition-specific changes in spatial organization. PO_SCPLOWOPARIC_SCPLOW jointly learns spatial metagenes - linear gene expression programs - and their spatial affinities across samples. Its key innovations include a differential prior to regularize spatial accordance and spatial downsampling to enable multiresolution, hierarchical analysis. Simulations show PO_SCPLOWOPARIC_SCPLOW outperforms existing methods on multisample and multi-resolution spatial metrics. Applications to real datasets uncover spatial metagene dynamics, spatial accordance, and cell identities. In mouse brain (STARmap PLUS), PO_SCPLOWOPARIC_SCPLOW identifies spatial metagenes linked to AD; in thymus (Slide-TCR-seq), it captures increasing colocalization of V(D)J recombination and T cell proliferation; and in ovarian cancer (CosMx), it reveals sample-specific malignant-immune interactions. Overall, PO_SCPLOWOPARIC_SCPLOW provides a general, interpretable framework for analyzing variation in multisample SRT.

bioinformatics↗

bioRxiv2025

The effects of E. granulosus PSCs proteins on host immune cells were elucidated through Transcriptomic and Metabolomic analyses

BackgroundEchinococcus granulosus (E. granulosus), a causative agent of zoonotic diseases, is widely prevalent across most regions and primarily affects vital organs such as the liver and lungs. The parasite secretes immunomodulatory substances, and its protoscolex proteins (PSCs) have been identified as potential diagnostic antigens and vaccine candidates. Although transcriptomics and metabolomics approaches have been employed to investigate echinococcosis, the impact of PSCs on the functionality of host immune cells and the expression of immunomodulatory-related genes remains largely unexplored. MethodsIn this study, immunofluorescence analysis was employed to determine the binding of PSCs to lymphocytes. The CCK-8 assay was utilized to evaluate the impact of varying concentrations of PSCs on cell viability, while ELISA was performed to quantify the levels of cytokines such as IL-9 and IL-4. Furthermore, by integrating LC-MS/MS-based metabolomics and RNA-Seq-based transcriptomics technologies, a systematic analysis was conducted to investigate the metabolic reprogramming and differential gene expression in lymphocytes following PSCs treatment, thereby elucidating the molecular mechanisms underlying its immune regulatory effects. ResultsPSCs proteins inhibited lymphocyte proliferation in a concentration-dependent manner, promoted IL-9 secretion at low concentrations, enhanced IL-4 expression at medium concentrations, and continuously up-regulated TGF-{beta} with increasing concentrations. Transcriptomic analysis identified 1,840 differentially expressed genes (991 up-regulated and 849 down-regulated), and KEGG enrichment analysis highlighted metabolic pathways, including phenylalanine metabolism. Gene Ontology (GO) analysis revealed that the functions of these genes were primarily associated with immunometabolic reprogramming and regulation of the intestinal barrier. Metabonomic profiling detected 12 significantly altered metabolites (8 up-regulated and 4 down-regulated). These findings suggest that PSCs reshape the host immune microenvironment via a metabolic-gene network. This study systematically elucidates how PSCs regulate immune cell function and metabolic homeostasis through multiple targets, providing novel insights into the immune escape mechanisms of parasites. ConclusionPSCs can induce host immune metabolic reprogramming, characterized by the activation of pyrimidine metabolism and the inhibition of bilirubin-mediated oxidative stress, through concentration-dependent regulation of Th9 cytokines (IL-9, IL-4/TGF-{beta}) and suppression of the PI3K-Akt signaling pathway. This process remodels the immune tolerance microenvironment. The aim is to elucidate the molecular mechanisms underlying parasite escape via multi-dimensional immunometabolic regulation, thereby providing a novel direction for the targeted treatment of echinococcosis. Author summaryE. granulosus is a zoonotic disease that can cause space-occupying lesions in the liver, lung and other organs, seriously threaten human health and cause economic losses in animal husbandry. It evades immune attack through a variety of mechanisms.This study investigates the regulatory effects of E. granulosus PSCs on host immune cell function, with a focus on their concentration-dependent influence on Th9 cell differentiation and cytokine expression, including IL-9. Through integrative analyses of transcriptomics and metabolomics, we elucidate the molecular mechanisms underlying immunometabolic reprogramming induced by PSCs. Our findings demonstrate that at low concentrations, PSCs promote the secretion of IL-9 associated with Th9 cells, upregulate IL-4/TGF-{beta} signaling, activate pyrimidine metabolism (leading to thymidine accumulation), enhance bile secretion pathways, and increase bilirubin levels to suppress oxidative stress and T-cell function, thereby establishing an immune-tolerant microenvironment. This research provides the first comprehensive illustration of immune microenvironment remodeling mediated by PSCs via multi-omics network regulation, offering novel insights into the treatment of cystic echinococcosis and host-parasite interactions.

immunology↗

bioRxiv2025

Novel HIV-1 fusion peptide immunogens using glycan-engineered alphavirus-like particles

Immunofocusing on conserved, subdominant epitopes is critical for vaccines against highly diverse viruses such as HIV-1, influenza, and SARS-CoV-2. The eight-residue N-terminus of the HIV-1 fusion peptide (FP) is one such example of a promising yet small target. We developed new FP immunogens using three alphavirus-like particles (VLPs) and introduced additional glycans to mask shared carrier-specific epitopes. In two independent guinea pig studies, sequential immunization with heterologous carriers enhanced FP-directed antibody titers, which were further improved with glycan engineering. Separately, using diverse FP variants sharing the same N-terminal six amino acids increased neutralizing antibody titers. When combined, these two strategies led to higher FP-directed titers and, after Env trimer boosting, induced FP-directed neutralizing antibodies against multi-clade wild-type HIV-1 in nearly all animals. These findings established the importance of minimizing recurrent off-target epitopes across immunizations and support the engineered VLPs as a promising platform for peptide immunization. HighlightsO_LINovel HIV-1 fusion peptide immunogens using glycan-engineered alphavirus-like particles C_LIO_LIImproved FP-directed response by minimizing recurrent carrier-specific epitopes across immunizations C_LIO_LIImproved neutralizing response by sequential immunization with diverse FP variants C_LIO_LIFP-directed antibodies neutralizing multi-clade wildtype viruses in nearly all animals C_LI

immunology↗

bioRxiv2025

DNA2 and MSH2 activity collectively mediate chemically stabilized G4 for efficient telomere replication

G-quadruplexes (G4s) are widely existing stable DNA secondary structures in mammalian cells. A long-standing hypothesis is that timely resolution of G4s is needed for efficient and faithful DNA replication. In vitro, G4s may be unwound by helicases or alternatively resolved via DNA2 nuclease mediated G4 cleavage. However, little is known about the biological significance and regulatory mechanism of the DNA2-mediated G4 removal pathway. Here, we report that DNA2 deficiency or its chemical inhibition leads to a significant accumulation of G4s and stalled replication forks at telomeres, which is demonstrated by a high-resolution technology: Single molecular analysis of replicating DNA (SMARD). We further identify that the DNA repair complex MutS (MSH2-MSH6) binds G4s and stimulates G4 resolution via DNA2-mediated G4 excision. MSH2 deficiency, like DNA2 deficiency or inhibition, causes G4 accumulation and defective telomere replication. Meanwhile, G4-stabilizing environmental compounds block G4 unwinding by helicases but not G4 cleavage by DNA2. Consequently, G4 stabilizers impair telomere replication and cause telomere instabilities, especially in cells deficient in DNA2 or MSH2.

molecular biology↗

bioRxiv2025

Cytokine-driven cellular polarization in preeclampsia revealed through the "Dictionary of immune responses"

BackgroundPreeclampsia (PE) is a pregnancy-related hypertensive disorder and a leading cause of maternal and perinatal mortality. Current treatments focus primarily on symptom management, as delivery remains the only definitive cure. This underscores the urgent need for innovative therapeutic strategies. Cytokines released by placental immune cells may contribute to the progression of PE and represent promising therapeutic targets. MethodsWe conducted single-cell sequencing on placental tissues obtained via cesarean section from patients with severe PE and cases of non-infectious preterm birth. Machine learning was applied to identify critical immune cells. Immune Response Enrichment Analysis was performed on these key cells to evaluate their polarization states and cytokine responses associated with PE. Additionally, we investigated cell-cell communications, key genes, and their related functions ResultsWe identified cell type-specific alterations in PE, including an increased proportion of CD4+ T cells polarized towards an IL-1- and IL-1{beta} enriched T4-c state. Altered SPP1 signaling between macrophages and CD4+ T cells was observed, indicating immune response dysregulation. Additionally, machine learning algorithms identified four hub genes, and six small-molecule drugs were predicted to hold therapeutic potential for PE. ConclusionsThis study emphasizes the importance of further understanding CD4+ T cell dynamics in preeclampsia, providing potential insights into the principles of placental immunity and contributing to the exploration of immunotherapeutic strategies

bioinformatics↗

bioRxiv2025

MouseGPT: A Large-scale Vision-Language Model for Mouse Behavior Analysis

Analyzing animal behavior is crucial in advancing neuroscience, yet quantifying and deciphering its intricate dynamics remains a significant challenge. Traditional machine vision approaches, despite their ability to detect spontaneous behaviors, fall short due to limited interpretability and reliance on manual labeling, which restricts the exploration of the full behavioral spectrum. Here, we introduce MouseGPT, a Vision-Language Model (VLM) that integrates visual cues with natural language to revolutionize mouse behavior analysis. Built upon our first-of-its-kind dataset--incorporating pose dynamics and open-vocabulary behavioral annotations across over 42 million frames of diverse psychiatric conditions--MouseGPT provides a novel, context-rich method for comprehensive behavior interpretation. Our holistic analysis framework enables detailed behavior profiling, clustering, and novel behavior discovery, offering deep insights without the need for labor-intensive manual annotation. Evaluations reveal that MouseGPT surpasses existing models in precision, adaptability, and descriptive richness, positioning it as a transformative tool for ethology and for unraveling complex behavioral dynamics in animal models.

animal behavior and cognition↗

bioRxiv2025

Targeted Protein Degradation by KLHDC2 Ligands Identified by High Throughput Screening

Proteolysis targeting chimeras (PROTACs) enable the selective and sub-stoichiometric elimination of pathological proteins, yet only two E3 ligases are routinely used for this purpose. Here, we expand the repertoire of PROTAC compatible E3 ligases by identifying a novel small molecule scaffold targeting the ubiquitin E3 ligase KLHDC2 using a fluorescence polarization-based high throughput screen. We highlight the utility of this ligand with the synthesis of PROTACs capable of potently degrading BRD4 in cells. This work affords additional chemical matter for targeting KLHDC2 and suggests a practical approach for identifying novel E3 binders by high throughput screening.

biochemistry↗

bioRxiv2025

Functional, Immunogenetic, and Structural Convergence in Influenza Immunity between Humans and Macaques

Human B cell immunity to the influenza hemagglutinin (HA) stem region, a universal influenza vaccine target, is often stereotyped and immunogenetically restricted, posing challenges for study outside humans. Here, we show that macaques vaccinated with a HA stem immunogen elicit human-like public B cell lineages targeting two major conserved sites of vulnerability, the central stem and anchor epitopes. Central stem antibodies were predominantly derived from VH1-138, the macaque homolog of human VH1-69, a VH-gene preferentially used in human central stem broadly neutralizing antibodies (bnAbs). Similarly, macaques produced anchor bnAbs with the human-like NWP motif. Both bnAb lineages were functionally and structurally analogous to their human counterparts, with recognition mediated largely by germline-encoded motifs. Thus the macaque immunoglobulin repertoire supports human-like public bnAb responses to influenza HA. Moreover, this underscores the utility of homologous germline-encoded immunity, suggesting that immune repertoires of macaques and humans may have been similarly shaped during evolution. HIGHLIGHTS[bullet] Functional human-like public antibody lineages can be elicited to HA stem supersites in macaques. [bullet]Macaque central stem bnAbs are predominantly derived from VH1-138, a VH-gene homologous to human VH1-69. [bullet]The human-like CDR L3 NWP anchor epitope-targeting lineage can be elicited in macaques. [bullet]Central stem and anchor bnAbs from humans and macaques engage their respective epitopes with atomic level similarity.

immunology↗

bioRxiv2025

GLYCO-2: a Tool to Quantify Glycan Shielding of Glycosylated Proteins with Improved Data Processing and Computation Speed

MotivationGlycans bound to glycoproteins mediate immune response, including antibody recognition and immune evasion. Previously, we developed an in silico tool GLYCO (GLYcan COverage) to quantify the glycan shielding of a protein surface, applying it to various studies. However, GLYCO lacks sufficient computational efficiency when analyzing larger datasets. ResultsHere we introduce GLYCO-2 which improves the computational speed by [~]4- fold compared to GLYCO by adopting a new analytical cylinder method with k-d trees. GLYCO-2 can calculate glycan shielding from a single coordinate file or from multiple frames derived from molecular dynamics simulations accounting for the inherent flexibility of oligosaccharides. We applied GLYCO-2 to quantify glycan shielding of influenza hemagglutinin (HA) proteins across diverse subtypes that infect humans, revealing an increasing trend in glycan shielding over time within each subtype, likely contributing to immune evasion. Overall, the enhanced computational efficiency of GLYCO-2 allows for faster and easier quantification of glycans, which contributes to the understand of glycan shielding effects in fields such as immunology and vaccine design. Availability and implementationGLYCO-2 is freely available at https://github.com/meteosR/GLYCO-2/ Contactmyungjin.lee@nih.gov or reda.rawi@nih.gov Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2025

HKU5 bat merbecoviruses use divergent mechanisms to engage bat and mink ACE2 as entry receptors

Identifying receptors for bat coronaviruses is critical for spillover risk assessment, countermeasure development, and pandemic preparedness. While Middle East respiratory syndrome coronavirus (MERS-CoV) uses DPP4 for entry, the receptors of many MERS-related betacoronaviruses remain unknown. The bat merbecovirus HKU5 was previously shown to have an entry restriction in human cells. Using both pseudotyped and full-length virus, we show that HKU5 uses Pipistrellus abramus bat ACE2 but not human ACE2 or DPP4 as a receptor. Cryo-electron microscopy (cryo-EM) analysis of the virus-receptor complex and structure-guided mutagenesis reveal a spike and ACE2 interaction that is distinct from other ACE2-using coronaviruses. MERS-CoV vaccine sera poorly neutralize HKU5 informing pan-merbecovirus vaccine design. Notably, HKU5 can also engage American mink and stoat ACE2, revealing mustelids as potential intermediate hosts. These findings highlight the versatility of merbecovirus receptor use and underscore the need for continued surveillance of bat and mustelid species.

microbiology↗

bioRxiv2025

Genetically Defined Organoid Models Reveal Mechanisms Driving Squamous Cell Neoplastic Evolution and Identify Potential Therapeutic Vulnerabilities

Upper aerodigestive squamous cell carcinoma (UASCC) is an aggressive and lethal neoplasm, with its early neoplastic transformation mechanisms remaining poorly understood. Here, we characterize over 25 genetically-defined organoid models derived from murine and human oral/esophageal tissues harboring key driver mutations. Double knockout of TP53 and CDKN2A induced morphological dysplasia, hyperproliferation, loss of squamous differentiation, and tumorigenicity, which were further exacerbated by additional driver mutations (e.g., PIK3CA, NOTCH1, KMT2C). Single-cell analysis revealed an expansion of quiescent basal cells and proliferative squamous cells, alongside a loss of differentiated squamous cells during malignant transformation. A distinct senescence program, regulated by ANXA1, was markedly diminished during early neoplastic evolution. Mechanistically, the ANXA1-SMAD3-p27KIP1 pathway was identified as a critical regulator of this senescence program, acting to suppress neoplastic features in organoid models. Lastly, our high-throughput, single-organoid-resolution drug screens unexpectedly revealed PIK3CA-driven organoids exhibited sensitivity to Mitomycin C and Onalespib. This study provides novel mechanistic insights into early neoplastic evolution and underscores the value of genetically-defined organoid models for investigating cancer biology and identifying targeted therapies.

cancer biology↗

bioRxiv2025

Harnessing landscape genomics to evaluate genomic vulnerability and future climate resilience in an East Asia perennial

In this era of rapid climate change, understanding the adaptive potential of organisms is imperative for buffering biodiversity loss. Genomic forecasting provides invaluable insights into population vulnerability and adaptive potential under diverse climatic conditions, thereby facilitating management interventions, bolstering population resilience, and shaping germplasm conservation strategies tailored to specific species. Here we integrated population genomics and landscape genomics approaches, leveraging single-nucleotide polymorphisms obtained through whole-genome resequencing of 43 Rheum palmatum complex populations, to pinpoint adaptive variation and its significance in the context of future climates, delineate seed zones, and establish guidelines for ex situ germplasm conservation to capture the majority of existing adaptive diversity. Our analysis unveiled that the species complex comprised two distinct genetic clusters, exhibiting differential climate adaptation and genomic vulnerabilities across its distribution range. We also determined that the species range could be subdivided into three distinct seed zones, with varying sample requirements per seed zone corresponding to differed conservation efforts. Overall, our findings provide a genome-wide perspective on climate adaptation and valuable insights into germplasm conservation strategies aimed at enhancing population resilience in future climates, serving as a blueprint for restoration plans of other vulnerable species.

evolutionary biology↗