Biology subjects

Yang, W.

Publications and source records attributed to Yang, W..

At least 91 records · Page 5Linked to original sources

bioRxiv2025

Site-Specific Immune and Stromal Architecture Drive Resistance to Trastuzumab Deruxtecan in HER2+ Metastatic Breast Cancer

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) that has demonstrated remarkable efficacy in HER2+ and HER2-low metastatic breast cancer (mBC). Yet, 40-50% of patients fail to respond, and mechanisms underlying resistance, particularly those involving the immune microenvironment, remain poorly understood. To address this gap, we conducted spatial proteomic profiling of metastatic lesions from 25 HER2+ mBC patients treated with T-DXd, using the Bruker GeoMX Digital Spatial Profiler (DSP) platform. Regions of interest (ROIs) were segmented by CD45 expression to distinguish immune-rich versus immune-poor compartments, and spatial marker expression was compared between responders (R) and non-responders (NR). Spearman correlation analysis was used to assess spatial coordination among HER2, fibronectin, and immune markers. Non-responders exhibited greater HER2 heterogeneity, lower CD45+ immune infiltration, and consistent upregulation of fibronectin and granzyme B. In both bone and brain metastases, NR tissues showed strong correlations between fibronectin and T cell markers, indicating spatial immune exclusion. In contrast, NR lymph node metastases displayed negative correlations between fibronectin and immune markers and uncoordinated B-T cell clustering, suggesting an alternative resistance mechanism rooted in immune disorganization rather than exclusion. Collectively, these results implicate HER2 heterogeneity, fibrotic immune exclusion, and immune suppression as key drivers of T-DXd resistance across metastatic sites. By integrating spatial proteomics with clinical outcomes, this study provides novel insights into the spatial immune landscape of ADC resistance and identifies actionable biomarkers for patient stratification and combination therapy design, laying a critical foundation for developing biomarker-guided therapies and personalized treatment strategies to overcome ADC resistance in metastatic breast cancer. Translational SignificanceT-DXd represents a major advance in antibody-drug conjugate (ADC) therapies to address HER2 heterogeneity in tumors through bystander killing. However, treatment options following resistance to T-DXd remain limited, leaving a critical unmet need. As new ADCs continue to emerge, resistance will likely remain a persistent challenge across tumor types. This work extends beyond T-DXd resistance--it provides a framework to address resistance mechanisms common to other ADCs. By investigating immune-mediated mechanisms of ADC resistance, this research identifies therapeutic targets that can be leveraged to develop new treatment strategies. By integrating spatial biology with clinical data, this study offers unprecedented insights into immune-tumor interactions within the resistant tumor microenvironment. This approach deepens mechanistic understanding and enables personalized treatment strategies guided by spatially resolved biomarkers. This novel combination of spatial mechanistic research with clinical data represents advancement toward overcoming ADC resistance and improving outcomes for patients with few therapeutic options.

cancer biology↗

bioRxiv2025

Identification of a RIPK2-Regulated Gene Signature as a Candidate Biomarker for RIPK2 Activity and Prognosis in Prostate Cancer

Receptor-interacting protein kinase 2 (RIPK2) has emerged as a promising drug target in various cancers, including prostate cancer (PC). However, the absence of reliable biomarkers to assess RIPK2 activity limits both patient selection for anti-RIPK2 therapies and treatment monitoring. To address this gap, we performed RNA-Seq analysis on PC cell lines (22Rv1, DU145, and PC3) with CRISPR/Cas9-mediated RIPK2 knockout (RIPK2-KO) using two independent guide RNAs. This analysis identified 13 candidate RIPK2-regulated genes, of which eight were validated by reverse transcription quantitative PCR (RT-qPCR). Furthermore, treatment with two distinct RIPK2 inhibitors significantly reduced RIPK2 signature scores in five independent PC cell lines in a dose- and/or time-dependent manner. Clinical association analyses revealed that high RIPK2 signature scores correlate with metastasis and worse biochemical recurrence-free, progression-free, disease-free, and overall survival, outperforming RIPK2 mRNA levels as a prognostic biomarker. This study establishes, for the first time, a RIPK2-regulated gene signature as a potential biomarker for RIPK2 activity and PC prognosis, warranting further validation in clinical specimens to provide a much-needed tool for patient stratification and response monitoring in RIPK2-targeted therapies.

cancer biology↗

bioRxiv2025

Structural Interactions of Ankyrin B with NrCAM and β2 Spectrin

Ank2 is a high confidence autism spectrum disorder (ASD) gene encoding the spectrin-actin scaffold protein Ankyrin B (AnkB). The 220 kDal isoform of AnkB has multiple functions including developmental spine pruning through L1 family cell adhesion molecules (L1-CAMs) and class 3 Semaphorins on dendrites of pyramidal neurons to achieve an appropriate excitatory balance in the neocortex. Molecular modeling employing AlphaFold was used to predict the structure and interactions of AnkB with the cytoplasmic domain of Neuron-glial Related L1-CAM (NrCAM), and with {beta}2-Spectrin. The validity of the models was assessed by analyzing protein-protein interactions by co-immunoprecipitation from HEK293 cell lysates after mutating key residues in AnkB predicted to impair these associations. Results revealed a pocket with critical residues in the AnkB membrane-binding domain that engages NrCAM at the conserved cytoplasmic motif FIGQY. Alphafold modeling of the AnkB/{beta}2-Spectrin complex also identified key interactions between the AnkB spectrin-binding domain and {beta}2-Spectrin repeats 14-15. Selected ASD-linked mutations in AnkB predicted to impact binding to NrCAM or {beta}2-Spectrin were then assayed for protein interactions. Maternally inherited ASD missense mutations AnkB A368G located in the NrCAM binding pocket and AnkB R977Q in the Zu51 subdomain disrupted associations with NrCAM and {beta}2-Spectrin, respectively. Moreover, AnkB A368G impaired the neuronal function of 220 kDal AnkB in Semaphorin 3F-induced spine pruning in mouse cortical neuron cultures. These new findings provide structural insights into the L1-CAM/AnkB complex and the molecular basis of ASD etiology associated with AnkB missense mutations.

neuroscience↗

bioRxiv2025

A SUMO-interacting motif in the guanine nucleotide exchange factor EPAC1 is required for subcellular targeting and function

Exchange protein directly activated by cAMP (EPAC1), a multifunctional intracellular cAMP receptor, dynamically localizes to various cellular loci, engaging with diverse molecular partners to maintain cellular homeostasis. The study investigates the role of the SUMO interacting motif (SIM) in the subcellular targeting and cellular functions of EPAC1. It reveals that the SIM is a critical structural element for EPAC1s association with RanBP2/Nup358, a nucleoporin of the cytoplasmic filament component of the nuclear pore complex (NPC). Mutational disruption of EPAC1 SIM interferes with EPAC1s ability to activate its canonical effectors, small GTPases, Rap1 and Rap2, and non-canonical functions, such as the formation of nuclear condensates and cellular SUMOylation. Because SIM is also directly involved in cAMP binding, RanBP2s association with EPAC1 with the SIM attenuates EPAC1s cAMP binding affinity to generate an EPAC1 signaling microdomain with reduced cAMP sensitivity around the NPC. The coupling between EPAC1s scaffold association and cAMP binding enables EPAC1 to tune its sensitivity to stress stimuli spatially depending on the cellular locations. These findings provide novel structural insights into EPAC1 signaling, highlighting the importance of SIM in EPAC1s cellular functions and potential novel strategies for therapeutically targeting EPAC1.

cell biology↗

bioRxiv2025

Control of leaflet movement pattern by a novel PP2C phosphatase DLM1 in Medicago truncatula

Sessile plants exhibit diverse movement behaviors that have long intrigued the scientists. The legume plants display a rhythmic leaflet movement pattern characterized by horizontal opening during the day and vertical closure at night. However, the underlying mechanisms remain largely enigmatic. Here, we isolated a mutant designated as dlm1 (downward leaflet movement1) from Medicago truncatula that displays leaflets downward opening during daytime while upward closure at night. Cellular analyses reveal that this aberrant phenotype correlates with abnormal volume changes of motor cells within the pulvinus. DLM1 exhibits high expression level in the motor organ pulvinus and encodes an unreported nuclear-localized PP2C phosphatase. Notably, phylogenetic analysis demonstrates that species exhibiting rhythmic leaflet movements consistently retain DLM1 homologs, suggesting the possibility of its functionally conserved role in regulating leaflets movement pattern. Structural characterization reveals that DLM1 possesses both phosphatase and kinase domains. Functional complementation assays demonstrate that the phosphatase domain is necessary and sufficient for maintaining the leaflet movement pattern. Collectively, our work uncovers a novel PP2C protein that governs the leaflet movement, providing mechanistic insights into this intriguing plant behavior.

plant biology↗

bioRxiv2025

The landscape of structural variation in pediatric cancer

Structural variants (SVs) account for over 60% of the driver variants in pediatric cancer, and in many cases act as the cancer initiating event. To study SVs from a pan-cancer perspective, we analyzed 1,616 pediatric cancer genomes in 16 major cancer types of hematological malignancies (n = 908), brain tumors (n = 183), and solid tumors (n = 525) and compared their profiles to those of 2,203 adult cancers. The SV burden varied [~]100-fold across pediatric cancer types and demonstrated an 8-to 16-fold reduction compared to adult brain and solid tumors but was comparable in pediatric versus adult hematological malignancies. Recurrent SV hotspots occurred uniquely in pediatric acute lymphoblastic leukemias (ALLs) in proximity to RAG-mediated recombination signal sequences (RSS) and disrupted multiple immune-related loci as well as 69 genes, which often involved cryptic RSS sites. By contrast, such hotspots affected only immune-related loci but not driver genes in adult lymphoid cancers. Eight SV signatures extracted from the cohort had varying distributions across cancer types, with clustered translocations reflecting templated insertions in osteosarcoma, and medium-sized deletions (10 kb to 1 Mb) enriched in cancers with RAG-mediated deletions. Intra-patient evolutionary analysis in 13 patients with multiple spatiotemporally distinct samples revealed that RAG-mediated recombination in leukemia and complex rearrangements in solid tumors occurred both early in disease initiation and continuously during later diversification, contributing to clonal heterogeneity. Finally, we found that both driver genes and fragile sites were the two genomic regions most frequently disrupted by SVs. The unique and diverse SV landscapes that emerged from this comprehensive analysis expand the scope of RSS-mediated mutagenesis in pediatric ALL and will be a valuable resource for guiding future functional studies and the design of clinical genomic testing in pediatric cancer.

cancer biology↗

bioRxiv2025

SKIDA1 transiently sustains MLL::ENL-Expressing hematopoietic progenitors during neonatal stages and promotes B-lineage priming

Infant leukemias arise as B-cell acute lymphocytic (B-ALL) or acute myeloid leukemia (AML). The majority are driven by chromosomal rearrangements of the MLL/ KMT2A gene (MLLr) and arise in utero, implying a fetal cell of origin. Fetal and neonatal hematopoietic progenitors have unique transcriptomes and epigenomes, raising the question of whether MLL fusion proteins activate distinct target gene profiles during these early stages of life. Here, we use a transgenic mouse model of MLL::ENL-driven leukemia to identify Skida1 as a target gene that is more highly induced in fetal and neonatal progenitors than in adult progenitors. SKIDA1 is highly expressed in human MLLr leukemias and the protein associates with the Polycomb Repressive Complex 2 (PRC2). We show that Skida1 is dispensable for normal hematopoiesis, but it promotes B-cell priming and maintains MLL::ENL-expressing hematopoietic stem cells (HSCs) and multipotent progenitor cells (MPPs) during neonatal development. Conditional deletion of Skida1 has no effect on normal HSC function, yet it impairs B-cell production from neonatal MLL::ENL-expressing HSCs while leaving myeloid leukemogenesis unaffected. Temporally-restricted targets of MLL fusion proteins, such as SKIDA1, can therefore tune cell fates at different ages, potentially influencing the types MLLr leukemias that arise at different ages.

cancer biology↗

bioRxiv2025

Imputation Disparities Driven by Recent Selectionand Their Impact on Disease Risk Estimation in East and Southeast Asian Populations

Using genotype data consisting of 8,316 individuals, we systematically evaluated imputation performance across six state-of-the-art reference panels for Chinese and Thai populations. A substantial proportion of variants identified through whole-genome sequencing, especially low-frequency variants, remained undetected by existing reference panels. In the Chinese population, the TOPMed panel required an R2 threshold of 0.60-0.70 to achieve comparable imputation accuracy of the ChinaMAP panel without R2 filtering, challenging the standard practice of applying a fixed R2 threshold for downstream analyses. Regional analysis highlighted the role of recent selection in imputation discrepancies and revealed an enrichment of immune-related genes in poorly imputed regions. In addition, we showed that the selection of reference panels and R2 thresholds could significantly influence estimation of polygenic risk score for disease prediction. These findings underscore the importance of developing ancestrally diverse reference panels and provide valuable guidelines for improving genotype imputation in East and Southeast Asian populations.

genomics↗

bioRxiv2025

Field Survey of Anopheles Mosquito and Their Culturable Gut Bacteria in the Border Regions of Yunnan Province, China

Despite the elimination of domestic malaria transmission within China, the border areas of Yunnan Province continue to face a heightened risk of imported cases due to the presence of diverse Anopheles mosquito species and the widespread burden of malaria in neighboring countries. While the mosquito gut microbiota offers a promising avenue for developing anti-malaria strategies, a meticulous investigation of the various Anopheles species and their associated gut microbiota in Yunnans border areas has yet to be undertaken. To address this gap, field surveys were conducted over the years 2020, 2021, and 2023. These surveys resulted in the collection of a substantial sample comprising 4,221 adult female mosquitoes spanning sixteen species with Anopheles sinensis identified as the predominant species. Furthermore, 741 cultivable strains of gut symbiotic bacteria were isolated and classified into four phyla comprising 109 genera with the composition of dominant bacteria varying annually. This study provides valuable insights into the population dynamics of malaria vectors in the border regions of Yunnan province, China, along with the intestinal bacteria they harbor including several bacterial species which exhibit promising anti-plasmodium effects. By leveraging the antagonistic effects of symbiotic bacteria against Plasmodium, our findings contribute to an ongoing global endeavor to develop innovative Anopheles management and malaria prevention strategies.

microbiology↗

bioRxiv2025

Functional landscape of circular RNAs in human cancer cells

Circular RNAs (circRNAs) constitute a novel class of noncoding RNAs showcasing distinct tissue- and cell-specific expression patterns. Despite the extensive profiling of circRNAs, their individual functions remain poorly understood. To fill this gap, we designed a genome-wide library of 65,300 shRNAs, targeting 9,663 clinically relevant circRNAs and 3,981 of their linear parental genes, and conducted functional screening in seven types of human cancer. We identified a total of 1,342 essential circRNAs (13.9% screened) that impact cell proliferation in at least one cell line, and in 96.5% of the cases, the linear counterparts are not essential. While a shared common subset emerges as functional regulators across all examined cell lines, the majority of circRNAs are functional in a cell type-specific manner. For a comprehensive presentation of the functional circRNA landscape in cancer, we introduce FunCirc, an online database encompassing functional circRNAs across cancer cell lines, coupled with circRNA expression profiles from diverse cancer and tissue types. Our work enhances the understanding of circRNA functions in cancer and provides the scientific community with a resource to further investigate their intricate roles.

cancer biology↗

bioRxiv2025

Circular RNA profiling and functional screening in breast cancer identify circNSD1 as a suppressor of tumor autophagy

Circular RNAs (circRNAs) have emerged as critical regulators of cell biology. However, their function in breast cancer remains elusive. Herein, through circRNA profiling of 38 breast tumors and 10 benign breast tissues, we identified 509 of differentially expressed circRNAs. Integration with transcriptome-wide functional screening of approximately 10,000 circRNAs pinpointed circNSD1(6) as a top ranked tumor suppressor in breast cancer. circNSD1(6) is downregulated in tumors and suppression of the circular form, but not the linear form, promotes breast cancer proliferation and tumor growth. Mechanistically, circNSD1(6) interacts with autophagy receptor SQSTM1/p62 and inhibits the oligomerization of p62, thereby suppressing p62 body formation and p62-dependent autophagy. Furthermore, circNSD1(6) ameliorates p62-mediated Keap1 sequestration, hence suppresses the Nrf2 pathway and oxidative stress tolerance. Our study provides a landscape view of the transcription and function of circRNA in breast cancer, and uncovers the crucial role of circNSD1(6) in autophagy and antioxidant stress.

cancer biology↗

bioRxiv2025

Bifunctional Phagocytic Synapse Enhancers for Cancer Immunotherapy

Immunotherapy profoundly impacted cancer treatments by harnessing the patients immune system. Phagocytosis, the process whereby immune cells engulf and destroy foreign particles or cells, plays a critical role in tumour cell clearance. Herein, we introduce a novel concept termed "ENPHASYS" - Enhancement of Phagocytic Synapses - designed to direct and amplify phagocytosis of cancer cells using heterobifunctional molecules named phagocytic synapse enhancers (PSEs). By engineering a de novo PD-L1 binder linked to a natural phagocytosis promoting peptide, tuftsin, the resulting PSE combines PD-L1 blockade with enhanced tumour cell phagocytosis; in addition, the PSEs induce macrophages to internalize a membrane or extracellular target. Intratumoural treatment of colorectal carcinoma- or glioblastoma-burdened immunocompetent animals resulted in beneficial overall survival, delayed tumour growth and a potent antitumor response driven by T-cell activation and TAM reprogramming, underpinning the translational relevance of ENPHASYS. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/642658v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@1673fd4org.highwire.dtl.DTLVardef@18fa319org.highwire.dtl.DTLVardef@11cf680org.highwire.dtl.DTLVardef@7b8784_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2025

Fetal context conveys heritable protection against MLL-rearranged leukemia that depends on MLL3

MLL rearrangements (MLLr) are the most common cause of congenital and infant leukemias. MLLr arise prior to birth and require few cooperating mutations for transformation, yet congenital leukemias are 10-fold less common than infant leukemias and >100-fold less common than childhood leukemias overall. This raises the question of whether mechanisms exist to suppress leukemic transformation during fetal life, thereby protecting the developing fetus from malignancy during a period of rapid hematopoietic progenitor expansion. Here, we use mouse models to show that fetal MLL::ENL exposure creates a heritable, leukemia-resistant state. MLL::ENL imposes a negative selective pressure on fetal hematopoietic progenitors. It leads to postnatal loss of self-renewal gene expression and enhanced myeloid differentiation that precludes transformation. These changes do not occur when MLL::ENL is induced shortly after birth, and transformation proceeds efficiently in this context. The fetal barrier to transformation is enforced by the histone methyltransferase MLL3. It can be overcome by cooperating mutations, such as NrasG12D, or through somatic or germline inactivation of MLL3. Heritable fetal protection against leukemic transformation may explain the low incidence of congenital leukemias in humans despite prenatal MLL rearrangement.

cancer biology↗

bioRxiv2025

Stathmin 1 regulates mitophagy and cellular function in hematopoietic stem cells

Stathmin 1 is a cytoplasmic phosphoprotein that regulates microtubule dynamics via promotion of microtubule catastrophe and sequestration of free tubulin heterodimers. Stathmin 1 is highly expressed in hematopoietic stem cells (HSCs), and overexpressed in leukemic cells, however its role in HSCs is not known. Herein, we found that loss of Stathmin 1 is associated with altered microtubule architecture in HSCs, and markedly impaired HSC function. Transcriptomic studies suggested alterations in oxidative phosphorylation in Stmn1-/- HSCs, and further mechanistic studies revealed defective mitochondrial structure and function in the absence of Stathmin 1 with increased ROS production. Microtubules associate with mitochondria and lysosomes to facilitate autophagosome formation and mitophagy, and indeed we found that this critical mitochondrial quality control process is impaired in Stathmin 1-deficient HSCs. Finally, stimulation of autophagy improved the colony forming ability of Stmn1-/- hematopoietic stem and progenitor cells. Together, our data identify Stathmin 1 as a novel regulator of mitophagy and mitochondrial health in HSCs. Key PointsO_LIThe microtubule regulating protein Stathmin 1 is highly expressed in HSPCs and promotes normal microtubule architecture. C_LIO_LILoss of Stathmin 1 in HSPCs leads to impaired autophagy with abnormal mitochondrial morphology, decreased respiratory capacity, and impaired cellular function. C_LI

cell biology↗

bioRxiv2025

Multimodal brain cell atlas across the adult macaque lifespan

High-throughput single-cell omics of non-human primate tissues present a remarkable opportunity to study primate brain aging. Here, we introduce a transcriptomic and chromatin accessibility landscape of 1,985,317 cells from eight brain regions of 13 cynomolgus female monkeys spanning adult lifespan including exceptionally old individuals up to 29-years old. This dataset uncovers dynamic molecular changes in critical brain functions such as synaptic communication and axon myelination, exhibiting a high degree of cell type and brain region specificity. We identify the multicellular networks of the pons and medulla as a previously unrecognized hotspot for aging. Furthermore, comparative analyses with human neurodegeneration datasets highlight both shared and distinct mechanisms contributing to aging and disease. In addition, we uncover transcription factors implicated in monkey brain aging and pinpoint aging-regulated loci linked to longevity and neurodegeneration. This spatiotemporal atlas will advance our understanding of primate brain aging and its broader implications for health and disease.

neuroscience↗

bioRxiv2025

High-Speed Neural Imaging with Multiplexed Miniature Two-Photon Microscopy (M-MINI2P)

Head-mounted miniaturized two-photon microscopes are powerful tools to record neural activity with cellular resolution deep in the mouse brain during unrestrained, free-moving behavior. Two-photon microscopy, however, is traditionally limited in imaging frame rate due to the necessity of raster scanning the laser excitation spot over a large field-of-view (FOV). Here, we present two multiplexed miniature two-photon microscopes (M-MINI2Ps) to increase the imaging frame rate while preserving the spatial resolution. Two different FOVs are imaged simultaneously and then demixed temporally or computationally. We demonstrate large-scale (500x500 m2 FOV) multiplane calcium imaging in visual cortex and prefrontal cortex in freely moving mice for spontaneous activity and auditory stimulus evoked responses. Furthermore, the increased speed of M-MINI2Ps also enables two-photon voltage imaging at 400 Hz over a 380x150 m2 FOV in freely moving mice. M-MINI2Ps have compact footprints and are compatible with the open-source MINI2P. M-MINI2Ps, together with their design principles, allow the capture of faster physiological dynamics and population recordings over a greater volume than currently possible in freely moving mice, and will be a powerful tool in systems neuroscience.

neuroscience↗

bioRxiv2025

The hollow truth: ethylene-triggered ROS, PCD, senescence, and autophagy drive hollow stem formation

Hollow stems have independently evolved multiple times across the plant kingdom, and play crucial roles in plant development and various environmental adaptations. However, the mechanisms underlying stem hollowness remain poorly understood. Water spinach (Ipomoea aquatica) is one of the few hollow-stemmed plants in the Convolvulaceae family, and its hollow stems are essential for thriving in aquatic environments. Using histochemical staining and transcriptome analysis, we identified programmed cell death (PCD) is involved in cavity formation of water spinach shoot tips. Single-cell transcriptome analysis further revealed that ethylene and reactive oxygen species (ROS) drive and regulate this process by activating transcription factors IaNAC074, IaNAC087, IaNAC029, IaNTL9, and IaTGA9, which initiate PCD, senescence, and autophagy, collectively controlling cell death. These findings were validated through treatments with ethylene and ROS reagents in water spinach and transient expression in tobacco. Additionally, transcriptomic data suggest that these mechanisms may also play a role in hollow stem formation in bamboo, highlighting the conservation of PCD regulatory mechanisms in plant development. This work not only fills a major knowledge gap in the adaptive mechanisms of hollow stem formation but also opens new avenues for agricultural and ecological applications, offering strategies to enhance crop tolerance to flooding and accelerate crop growth.

plant biology↗

bioRxiv2025

Leopard Cats Occupied Human Settlements in China for 3,500 years before the Arrival of Domestic cats in 600-900 CE around the Tang Dynasty

The earliest cats in human settlements in China were not domestic cats (Felis catus), but native leopard cats (Prionailurus bengalensis). To trace when and how domestic cats arrived in East Asia, we analyzed 22 feline bones from 14 sites across China spanning 5,000 years. Nuclear and mitochondrial genomes revealed that leopard cats began occupying anthropogenic scenes around 5,400 years ago and last appeared in 150 CE. Following several centuries gap of archeological feline remains, the first known domestic cat (706-883 CE) in China was identified in Shaanxi during the Tang Dynasty. Genomic analysis suggested a white or partially white coat and a link to a contemporaneous domestic cat from Kazakhstan, indicating a likely dispersal route via the Silk Road. The two felids once independently occupied ancient anthropogenic environments in China but followed divergent paths and reached different destinations in human-animal interactions.

evolutionary biology↗