Biology subjects

Choe, K.

Publications and source records attributed to Choe, K..

6 recordsLinked to original sources

bioRxiv2026

Intravital single-cell behavior profiling reveals disrupted germinal center B cell motility and interactions by EZH2 gain-of-function mutation

Germinal center (GC) B-cells give rise to the majority of non-Hodgkin lymphomas, underscoring the need to pinpoint critical processes that initiate and drive lymphomagenesis. Lymphoma driver mutations can alter GC B cell functions and B cell fate decisions. Here, we studied how EZH2 oncogenic mutation in GC B cells alters cellular motility and interactions with T follicular helper (Tfh) cells and follicular dendritic cells (FDCs) to determine B cell fate. By combining intravital imaging, single-cell behavior analyses, and RNA sequencing, we uncover how lymphoma-associated EZH2 mutations reprogram the behaviors of GC B cells in vivo. We found that EZH2 mutations increased single-cell motility speeds and morphological plasticity of GC B cells, redirecting migration toward the FDC-rich light zone subregions rather than to the dark zone. Although mutant EZH2 GC B cells exhibited normal engagement quality with FDCs, they showed shorter interaction times and reduced surface engagement with Tfh cells. Notably, EZH2 mutant B cells required prior contact with FDC before engaging with Tfh cells, thus impairing DZ recycling. This motility phenotype scaled with local mutant clone abundance, suggesting a behavioral strategy underlying how mutant cells outcompete WT cells. Lastly, we developed scMOTIPh, a computational framework that integrates single-cell behavioral features with transcriptomic profiles. Applying scMOTIPh to mutant GC B cells within the FDC-rich zone revealed enhanced ATP production, metabolic and antigen-presentation programs, and suppression of cell-death pathways, which is consistent with a tendency for malignant transformation and survival fitness. These findings provide an in vivo, single-cell view of how an epigenetic lesion rewires the local microenvironment by modulating single-cell behaviors within native GCs, revealing a dynamic mechanism for early lymphomagenesis.

immunology↗

bioRxiv2026

The TIRR–53BP1 axis controls PLK1 spatiotemporal regulation during mitosis

p53-binding protein 1 (53BP1) is a key mediator of the DNA damage response and genome stability. While its interphase function is well-characterized, its mitotic role remains less understood. Here we show that aberrant activation of 53BP1 through the loss of its negative regulator, TIRR, leads to mitotic abnormalities including altered spindle geometry, kinetochore-microtubule (k-MT) attachment errors and whole chromosome missegregation. We demonstrate that loss of TIRR results in excess interaction between 53BP1 and the key mitotic kinase Polo-like kinase 1 (PLK1), altering PLK1s activation, spatial distribution, and its interaction with known PLK1 substrates at multiple mitotic stages. Moreover, due to PLK1s established role in CENP-A loading, hyperactivation of 53BP1 compromises CENP-A loading, triggers gradual loss of CENP-A from centromeres and generates severe kinetochore assembly defects. These findings uncover a non-canonical mitotic function of 53BP1 as a key regulator of PLK1 activity and chromosome segregation fidelity.

Cell Biology↗

bioRxiv2025

Data-driven simulations elucidate how lymphocyte motility behaviors drive cell-cell interactions within germinal centers

Lymphocytes rely on cell motility to surveil immune microenvironments and engage in contact-mediated interactions with other cells as part of the adaptive immune response. Within the germinal center (GC) light zone, germinal center B-cells (GCBs) and T-follicular helper cells (Tfhs) engage in cell-cell interactions that enable antibody affinity maturation. The number and duration of GCB-Tfh interactions correlate with the success of the germinal center in effectively generating antibodies that can bind and neutralize antigens. Prior studies have shown that GCBs and Tfhs exploit distinct motility patterns to surveil the GC light zone and engage in these cell-cell interactions. However, the quantitative relationship between lymphocyte motility parameters (such as speed and tortuosity) and GCB-Tfh interactions has not been systematically explored. Here, we analyzed single-cell trajectories of GCBs and Tfhs from two-photon intravital microscopy videos of GCs within mouse popliteal lymph nodes. We found that these cells exhibit seven distinct motility behaviors, each with characteristic speeds and tortuosities. GCBs tended to move in slow and tortuous paths, while Tfhs adopted faster and more directed trajectories. We then developed a three-dimensional agent-based model (ABM) to simulate these experimentally-observed GCB and Tfh motility behaviors and predict their impact on GCB-Tfh interactions. Using the ABM, we found that the baseline motility behaviors of GCBs and Tfhs allow GCBs to maximize interactions with distinct Tfhs in a confined space.

systems biology↗

bioRxiv2023

Comparison of New and Old BacT/Alert Aerobic Bottles for Detection of Candida spp.

PurposeA new version of aerobic blood culture media has been developed for the BacT/Alert (bioMerieux) blood culture system. We evaluated the TTD and yeast cell counts in positive blood cultures for each Candida spp. according to changes in media. MethodsIsolates from defibrinated horse blood were inoculated into three types of bottles: the old version of FA Plus (Old FA Plus), New FA Plus, and FN Plus. All bottles were incubated in the BacT/Alert Virtuo blood culture system. The TTD was monitored for each bottle, and yeast cell counts were performed immediately after testing positive, determined via the plate count method. Clinical retrospective data of the candidemia samples before and after aerobic bottle change also were analyzed. ResultsThe mean TTD was 51.2 hours in the Old FA Plus bottles versus 19.5 hours in the New FA Plus bottles (P < 0.001) for Candida glabrata, and standard and clinical strains showed similar results. C. albicans (27.6 to 25.1 hours) and C. guilliermondii (28.8 to 27.3 hours) had shorter TTDs. However, C. auris (25.6 to 28.1 hours) had a longer TTD in the New FA Plus bottle. The retrospective clinical analysis showed a significant decrease in TTD (45.0 to 19.4 hours) for C. glabrata, which is consistent with our simulated study. ConclusionThis study shows that the TTD of C. glabrata was markedly reduced in the New FA Plus bottle due to the optimized growth performance. The reduction of TTD enables faster detection and therapeutic approach for C. glabrata infections.

microbiology↗

bioRxiv2020

Stepwise transmigration cascade of T and B cells through the perivascular channel in lymph node high endothelial venules

High endothelial venules (HEVs) effectively recruit circulating lymphocytes from the blood to lymph nodes. HEVs have endothelial cells (ECs) and perivascular sheaths consisting of fibroblastic reticular cells (FRCs). Many studies have characterized the multiple steps of lymphocyte migration interacting with ECs at the luminal side of HEVs. However, post-luminal migration steps are not well elucidated. Herein, we performed intravital imaging to investigate post-luminal T and B cell migration, consisting of trans-EC migration, crawling in the perivascular channel (a narrow space between ECs and FRCs) and trans-FRC migration. The post-luminal migration of T cells occurred in a PNAd-dependent manner. Remarkably, we found hot spots for the trans-EC and trans-FRC migration of T and B cells. Interestingly, T and B cells preferentially shared trans-FRC migration hot spots but not trans-EC migration hot spots. Furthermore, the trans-FRC T cell migration was confined to fewer sites than trans-EC T cell migration, and trans-FRC migration of T and B cells preferentially occurred at FRCs covered by CD11c+ dendritic cells in HEVs. These results suggest that HEV ECs and FRCs with perivascular DCs delicately regulate T and B cell entry into lymph nodes.

immunology↗

bioRxiv2018

Molecular Subtypes of Anaplastic Gliomas Identified with Somatic-Mutation and Pathway Based Gene Signature

PurposeAnaplastic gliomas constitute heterogeneous population with variable outcomes and no consensus on therapeutic approach. Molecular profiling may provide prognostication beyond clinical and pathologic factors and help guide treatment decisions.\n\nExperimental DesignThe Cancer Genome Atlas (TCGA) was utilized to derive a 39-gene low grade glioma-specific gene signature. Consensus clustering based on expression of the signature identified subgroups for 176 patients with anaplastic glioma from TCGA. Overall survival (OS) was analyzed for each subgroup. A total of 68 patients from Repository for Molecular Brain Neoplasia Data (REMBRANDT) were used as an independent validation dataset.\n\nResultsConsensus clustering separated the TCGA group into two distinct cohorts. The OS was significantly different between two subgroups, 20 vs. 67 months (p<0.001). On univariate analysis, the molecular subgroup, age, KPS, IDH1/2 mutation, 1p19q-co-deletion, chemotherapy, and use of both chemotherapy and radiation-therapy were significantly associated with OS. On multivariable analysis, the molecular subgroup remained significant with HR of 2.6 (p=.047, 95%CI [1.01-6.68]). In an independent validation with REMBRANDT, consensus clustering based on the signature successfully identified similarly poor prognostic subgroup with median survival of 14 months and concordance of expression patterns in 21 of the genes.\n\nConclusionExpression patterns of the 39 gene stratified anaplastic gliomas into two distinct subgroups with substantially different OS. This molecular prognostication was validated in an external dataset. Utilization of molecular subgroup, in addition to known prognostic factors may help define those requiring aggressive therapeutic intervention. Characteristic genes within the poor prognostic group may represent potential targets for therapeutic intensification.\n\nSource code and dataset used in this work is available for reviewers at: https://www.taehyunlab.org/ntripath\n\nImportance of the studyDespite the revolution of tailored therapy, anaplastic gliomas represent a category of tumors without clear treatment recommendations. While current prognostic factors help guide therapy recommendations, further refinement with the addition of molecular markers can help physicians with treatment recommendations. In this study, we developed a 39 gene prognostic gene signature by utilizing Pan-Cancer TCGA mutation profiles of over 5,000 patients across 19 different TCGA cancer types to stratify patients with anaplastic gliomas. We performed consensus clustering based on gene expression profiles of our 39-gene signature without any consideration of clinical factors or outcomes to TCGA anaplastic gliomas patients as well as an independent dataset and successfully identified two molecular subgroups with distinct clinical outcome. We found that subgroups have remarkably different survivals with a clear poor prognostic group. Furthermore, the poor prognostic group showed significant benefits for aggressive multimodality therapy, justifying the use of intensive therapy based on molecular stratification.

genomics↗