研究成果

Oct, 2022
Hsueh-Ping Chu
Alternative Lengthening of Telomeres (ALT) utilizes a recombination mechanism and break-induced DNA synthesis to maintain telomere length without telomerase, but it is unclear how cells initiate ALT. TERRA, telomeric repeat-containing RNA, forms RNA:DNA hybrids (R-loops) at ALT telomeres. We show that depleting TERRA using an RNA-targeting Cas9 system reduces ALT-associated PML bodies, telomere clustering, and telomere lengthening. TERRA interactome reveals that TERRA interacts with an extensive subset of DNA repair proteins in ALT cells. One of TERRA interacting proteins, the endonuclease XPF, is highly enriched at ALT telomeres and recruited by telomeric R-loops to induce DNA damage response (DDR) independent of CSB and SLX4, and thus triggers break-induced telomere synthesis and...
Sep, 2022
Chia-Lang Hsu and Hsueh-Fen Juan
The small nucleolar RNA host gene 1 (SNHG1) is a novel oncogenic long non-coding RNA (lncRNA) aberrantly expressed in different tumor types. We previously found highly expressed SNHG1 was associated with poor prognosis and MYCN status in neuroblastoma (NB). However, the molecular mechanisms of SNHG1 in NB are still unclear. Here, we disrupted endogenous SNHG1 in the MYCN-amplified NB cell line SK-N-BE(2)C using the CRISPR/Cas9 system and demonstrated the proliferation and colony formation ability of SNHG1-knowndown cells were suppressed. The transcriptome analysis and functional assays of SNHG1-knockdown cells revealed SNHG1 was involved in various biological processes including cell growth, migration, apoptosis, cell cycle, and reactive oxygen species (ROS). Interestingly, the expression...
Sep, 2022
Chia-Lang Hsu and Pei-Lung Chen
Adaptive immune receptor repertoire (AIRR) is encoded by T cell receptor (TR) and immunoglobulin (IG) genes. Profiling these germline genes encoding AIRR (abbreviated as gAIRR) is important in understanding adaptive immune responses but is challenging due to the high genetic complexity. Our gAIRR Suite comprises three modules. gAIRR-seq, a probe capture-based targeted sequencing pipeline, profiles gAIRR from individual DNA samples. gAIRR-call and gAIRR-annotate call alleles from gAIRR-seq reads and annotate whole-genome assemblies, respectively. We gAIRR-seqed TRV and TRJ of seven Genome in a Bottle (GIAB) DNA samples with 100% accuracy and discovered novel alleles. We also gAIRR-seqed and gAIRR-called the TR and IG genes of a subject from both the peripheral blood mononuclear cells (PBMC...
Jun, 2022
Hsueh-Fen Juan
The tumor microenvironment (TME), which comprises cellular and noncellular components, is involved in the complex process of cancer development. Emerging evidence suggests that mesenchymal stem cells (MSCs), one of the vital regulators of the TME, foster tumor progression through paracrine secretion. However, the comprehensive phosphosignaling pathways that are mediated by MSC-secreting factors have not yet been fully established. In this study, we attempt to dissect the MSC-triggered mechanism in lung cancer using quantitative phosphoproteomics. A total of 1958 phosphorylation sites are identified in lung cancer cells stimulated with MSC-conditioned medium. Integrative analysis of the identified phosphoproteins and predicted kinases demonstrates that MSC-conditioned medium functionally...
May, 2022
Hsueh-Fen Juan and Chien-Yu Chen
With the proliferation of genomic sequence data for biomedical research, the exploration of human genetic information by domain experts requires a comprehensive interrogation of large numbers of scientific publications in PubMed. However, a query in PubMed essentially provides search results sorted only by the date of publication. A search engine for retrieving and interpreting complex relations between biomedical concepts in scientific publications remains lacking. Here, we present pubmedKB, a web server designed to extract and visualize semantic relationships between four biomedical entity types: variants, genes, diseases, and chemicals. pubmedKB uses state-of-the-art natural language processing techniques to extract semantic relations from the large number of PubMed abstracts...
May, 2022
Te-Lun Mai
Circular RNAs (circRNAs) are a class of non-coding RNAs formed by pre-mRNA back-splicing, which are widely expressed in animal/plant cells and often play an important role in regulating microRNA (miRNA) activities. While numerous databases have collected a large amount of predicted circRNA candidates and provided the corresponding circRNA-regulated interactions, a stand-alone package for constructing circRNA-miRNA-mRNA interactions based on user-identified circRNAs across species is lacking. We present CircMiMi (circRNA-miRNA-mRNA interactions), a modular, Python-based software to identify circRNA-miRNA-mRNA interactions across 18 species (including 16 animals and 2 plants) with the given coordinates of circRNA junctions. The CircMiMi-constructed circRNA-miRNA-mRNA interactions are...
Apr, 2022
Jian-Da Lin
Single-cell transcriptomic data identifies major activation paths of monocyte-derived macrophages as a framework for inflammatory tissue macrophages.
Apr, 2022
Hsueh-Fen Juan
Mitochondria are crucial organelles that provide energy via oxidative phosphorylation in eukaryotic cells and also have critical roles in growth, division, and the cell cycle, as well as the rapid adaptation required to meet the metabolic needs of the cell. Mitochondrial processes are highly dynamic; fusion and fission can vary with cell type, cellular context, and stress levels. Accumulating evidence demonstrates that an imbalance in mitochondrial dynamics leads to death in numerous types of human cancer cells. Therefore, modulating mitochondrial dynamics could be a therapeutic target. In this review, we provide an overview of the protein interaction networks involved in mitochondrial dynamics as effective and feasible drug targets and discuss the related potential therapeutic strategies...
Feb, 2022
Hsueh-Fen Juan
Single-cell RNA sequencing (scRNA-seq) approach can broadly and specifically evaluate the individual cells with minimum detection bias. To explore the individual compositional and transcriptional alteration of intestinal leukocytes in the Dual Specificity Phosphatase six knockout (D6KO) mice, we performed a scRNA-seq followed by the cell type annotation based on ImmGen database. Composition assessments found that D6KO-derived intestinal leukocytes tend to stay inactivate or immature status. The enrichment analysis showed that D6KO-derived intestinal leukocytes are less sensitive to microbes. The mod PhEA phenotypic analysis showed that the D6KO leukocytes may link to not only immune-associated but also diverse previously non-immune-related diseases. Integrating our dataset with the...
Feb, 2022
Hsueh-Fen Juan
The hourglass model is a popular evo-devo model depicting that the developmental constraints in the middle of a developmental process are higher, and hence the phenotypes are evolutionarily more conserved, than those that occur in early and late ontogeny stages. Although this model has been supported by studies analyzing developmental gene expression data, the evolutionary explanation and molecular mechanism behind this phenomenon are not fully understood yet. To approach this problem, Raff proposed a hypothesis and claimed that higher interconnectivity among elements in an organism during organogenesis resulted in the larger constraints at the mid-developmental stage. By employing stochastic network analysis and gene-set pathway analysis, we aim to demonstrate such changes of...

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