Biology subjects

Xia, E.

Publications and source records attributed to Xia, E..

5 recordsLinked to original sources

bioRxiv2026

Intravenous anti-abeta immunotherapy acutely increases cerebral amyloid angiopathy and vascular damages in APOE4 mice

Anti-A{beta} immunotherapies for Alzheimers Disease (AD) have high rates of amyloid-related imaging abnormalities (ARIA), an adverse side effect with markedly higher rates in APOE4 carriers. We developed a mouse model of ARIA centered on human APOE3 and APOE4 genotypes with amyloidosis (5xFAD transgene) and microglia tagged with green fluorescent protein (from the CX3CR1 promoter). We measured acute changes following a single intravenous treatment with 3D6 anti-A{beta} immunotherapy. Across 82 mice, APOE4 mice showed stepwise reductions in the number of plaques from one to ten days, with significant reductions in the subiculum (48%) and thalamus (40%) at ten days. There was no significant reduction in APOE3 mice. There was a concomitant significant increase in deposition of cerebral amyloid angiopathy (CAA) in APOE4 mice at one (76%) and three (51%) days in leptomeningeal vessels. The increased CAA correlated with a significant 189% increase in A{beta} within microglia of APOE4 (but not APOE3) mice at one day. Smooth muscle actin staining showed significant 58% reduction near CAA. MRI analysis revealed a significant 32% increase in microhemorrhages ten days following treatment. These data demonstrate an APOE4-specific redistribution of parenchymal amyloid to CAA by 3D6 within days, leading to increased vascular damages associated with ARIA.

neuroscience↗

bioRxiv2025

Pangenome analyses of tea plant reveal structural variations driven gene expression alterations and agronomic trait diversification

Tea plants, one of the worlds most economically significant beverage crops, exhibit extensive genetic diversity and a rich array of secondary metabolites. While structural variations (SVs) are key drivers of phenotypic innovation, their regulatory roles in transcriptional networks and agronomic trait diversification remain underexplored in this perennial crop. We constructed a pangenome from 21 representative tea accessions and their wild relatives. Comparative analysis revealed that wild relatives harbor a greater abundance of gibberellin-related genes, whereas cultivated accessions exhibit an expansion of defense-related genes. We identified 522,428 non-redundant SVs, primarily insertions/deletions (73.56%), which were enriched in promoter regions. These SVs influenced the expression of genes governing flavor compounds, including those involved in flavonoid, amino acid, and terpenoid biosynthesis. Population SV analysis of 275 tea accessions uncovered three haplotypes in the ANS3 gene promoter region, with Hap1, containing a 192 bp insertion, predominantly found in wild relatives but largely lost in modern cultivars. This insertion enhanced CtANS3 expression, increasing anthocyanin accumulation. Additionally, a 159 bp insertion in the CtLRR1 promoter reduced resistance to Colletotrichum gloeosporioides in wild relatives. Our findings underscore SVs as pivotal regulators of genomic diversity, flavor differentiation, and adaptive evolution in tea plant domestication.

genomics↗

bioRxiv2024

Root-specific secondary metabolism at the single-cell level: a case study of theanine metabolism and regulation in the roots of tea plants (Camellia sinensis)

Root-synthesized secondary metabolites are critical quality-conferring compounds of foods, plant-derived medicines, and beverages. However, information at a single-cell level on root-specific secondary metabolism remains largely unexplored. L-theanine, an important quality component of tea, is primarily synthesized in roots, from which it is then transported to new shoots of tea plant. In this study, we present a single-cell RNA sequencing (scRNA-seq)-derived map for the tea plant root, which enabled cell-type-specific analysis of glutamate and ethylamine (two precursors of theanine biosynthesis) metabolism, and theanine biosynthesis, storage, and transport. Our findings support a model in which the theanine biosynthesis pathway occurs via multicellular compartmentation and does not require high co-expression levels of transcription factors and their target genes within the same cell cluster. This study provides novel insights into theanine metabolism and regulation, at the single-cell level, and offers an example for studying root-specific secondary metabolism in other plant systems.

plant biology↗

bioRxiv2021

Inactivation of the Hippo Tumor Suppressor Pathway Promotes Melanoma

Human melanomas are commonly driven by activating mutations in BRAF, which promote melanocyte proliferation through constitutive stimulation of the MAPK pathway. However, oncogenic BRAF alone is insufficient to promote melanoma; instead, its expression merely induces a transient burst of proliferation that ultimately ceases with the development of benign nevi (i.e. moles) comprised of growth-arrested melanocytes. The tumor suppressive mechanisms that induce this melanocytic growth arrest remain poorly understood. Recent modeling studies have suggested that the growth arrest of nevus melanocytes is not solely due to oncogene activation in individual cells, but rather due to cells sensing and responding to their collective overgrowth, similar to what occurs in normal tissues. This cell growth arrest is reminiscent of the arrest induced by activation of the Hippo tumor suppressor pathway, which is an evolutionarily conserved pathway known to regulate organ size. Herein, we demonstrate that oncogenic BRAF signaling activates the Hippo pathway in vitro, which leads to inhibition of the pro-growth transcriptional co-activators YAP and TAZ, ultimately promoting the growth arrest of melanocytes. We also provide evidence that the Hippo tumor suppressor pathway is activated in growth-arrested nevus melanocytes in vivo, both from single-cell sequencing of mouse models of nevogenesis and human tissue samples. Mechanistically, we observe that oncogenic BRAF promotes both ERK-dependent alterations in the actin cytoskeleton and whole-genome-doubling events, and that these two effects independently promote Hippo pathway activation. Lastly, we demonstrate that abrogation of the Hippo pathway, via melanocyte-specific deletion of the Hippo kinases Lats1/2, enables oncogenic BRAF-expressing melanocytes to bypass nevus formation, thus leading to the rapid onset of melanoma with 100% penetrance. This model is clinically relevant, as co-heterozygous loss of LATS1/2 is observed in [~]15% of human melanomas. Collectively, our data reveal that the Hippo pathway enforces the stable growth arrest of nevus melanocytes and therefore represents a critical and previously unappreciated barrier to melanoma development.

cancer biology↗

bioRxiv2018

Unperturbed Expression Bias of Imprinted Genes in Schizophrenia

How gene expression correlates with schizophrenia across individuals is beginning to be examined through analyses of RNA-seq from post-mortem brains of individuals with disease and control brains. Here we focus on variation in allele-specific expression, following up on the Common Mind Consortium (CMC) RNA-seq experiments of nearly 600 human dorsolateral prefrontal cortex (DLPFC) samples. Analyzing the extent of allelic expression bias--a hallmark of imprinting--we find that the number of imprinted human genes is consistent with lower estimates ({approx}0.5% of all genes) and thus contradicts much higher estimates. Moreover, the handful of putatively imprinted genes are all in close genomic proximity to known imprinted genes. Joint analysis of the imprinted genes across hundreds of individuals allowed us to establish how allelic bias depends on various factors. We find that age and genetic ancestry have gene-specific, differential effect on allelic bias. In contrast, allelic bias appears to be independent of schizophrenia.

genomics↗