Biology subjects

Lee, W. J.

Publications and source records attributed to Lee, W. J..

5 recordsLinked to original sources

bioRxiv2024

Morphological and Molecular Phylogenetic Characterization of Three New Marine Goniomonad Species

Goniomonads are commonly found heterotrophic biflagellates in both marine and freshwater environments. Despite the high genetic diversity inferred from 18S rDNA data, many goniomonad species remain undescribed. In this study, we established a total of 21 marine goniomonad culture strains, and from these, describe three new species by using light microscopy, electron microscopy, and 18S rDNA phylogeny. Molecular sequence analyses suggest the presence of several distinct sub-lineages within the marine goniomonad clade. Two of these are Goniomonas ulleungensis sp. nov. and G. lingua sp. nov., which are similar in size, flagellar length, appendage & orientation and by having a tongue-like protrusion at the anterior. The two species can be differentiated by the periplast plate pattern with G. ulleungensis displaying one additional plate on the right side. G. duplex sp. nov. differed from these two species by having two unequal flagella with the longer one trailing posteriorly and having the opposite cell orientation when skidding. Comparative analyses of five marine goniomonad species showed that genetically distinct goniomonad groups can be delineated by morphological data as well, and of several morphological features that are of taxonomic utility, the periplast plate pattern, observable by SEM, is particularly informative in goniomonad taxonomy.

evolutionary biology↗

bioRxiv2024

RBP4 functions as an antagonistic ligand of orphan DR6

Death receptor (DR) is a unique transmembrane receptor mediating extrinsic factor-induced programmed cell death pathways. For most DRs, the regulatory mechanism has been revealed to involve agonistic death ligand (e.g., TRAIL, TNF-)-driven receptor clustering and activation, offering an in-depth understanding of the mechanistic basis for cell death regulation and therapeutic strategies. However, only death receptor 6 (DR6) remains orphan, and its molecular mechanism is poorly understood. Here, we identified retinol binding protein 4 (RBP4), a major vitamin-A carrier protein, as an antagonistic ligand of DR6. Single-molecule photobleaching and single-receptor tracking analyses revealed that RBP4 drives DR6 dimerization on the plasma membrane to prevent DR6 prodegenerative heterointeractions and consequent neurodegenerative processes. DR6 homodimerization predominantly depends on an extracellular intrinsically disordered region, allowing the agonistic propensity of increasing Ca2+ levels. Collectively, our study establishes the distinct molecular mechanism of DR6 and highlights the non-canonical role of RBP4 as a cell death regulator.

molecular biology↗

bioRxiv2024

A browser-based platform for storage, visualization, and analysis of large-scale 3D images in HPC environments

High-throughput microscopy necessitates 3D image storage, visualization, and analysis in terabyte to petabyte scales. Centralized high-performance computing (HPC) infrastructure provides the resources, but interfacing software is limited. We developed an extensible platform with a scalable image storage format (SISF) and content delivery network (CDN) to enable fast, random access to compressed data. Additionally, we built a cloud-based nTracer2 software to annotate neuron morphology from SISF images in a web browser.

bioinformatics↗

bioRxiv2024

Artifact-Minimized High-Ratio Image Compression with Preserved Analysis Fidelity

Recent advances in microscopy have pushed imaging data generation to an unprecedented scale. While scientists benefit from higher spatiotemporal resolutions and larger imaging volumes, the increasing data size presents significant storage, visualization, sharing, and analysis challenges. Lossless compression typically reduces the data size by <4 fold, whereas lossy compression trades smaller data size for the loss of a precise reconstruction of the original data. Here, we develop a novel quantization method and an artifact metric for automated compression parameter optimization that preserves information fidelity. We show that, when combined with the AV1 video codec, we achieve tens to ten thousand folds of data compression while introducing negligible visual defects or quantification errors in single-molecule localization and segmentation analyses. We developed an HDF5 filter with FFMPEG library support for convenient community adaptation. For instance, HDF5-enabled ImageJ plugins can now be seamlessly extended to support AV1 compression and visualization to handle terabyte-scale images.

bioinformatics↗

bioRxiv2023

Multimodal decoding of human liver regeneration

The liver has a unique ability to regenerate1,2, however in the setting of acute liver failure (ALF) this regenerative capacity is often overwhelmed and emergency liver transplantation is the only curative option3-5. To advance our understanding of human liver regeneration and to inform design of pro-regenerative therapies, we use paired single-nuclei RNA sequencing (snRNA-seq) combined with spatial profiling of healthy and ALF explant human livers to generate the first single-cell, pan-lineage atlas of human liver regeneration. We uncover a novel ANXA2+ migratory hepatocyte subpopulation which emerges during human liver regeneration, and a corollary migratory hepatocyte subpopulation in a mouse model of acetaminophen (APAP)-induced liver regeneration. Importantly, interrogation of necrotic wound closure and hepatocyte proliferation across multiple timepoints following APAP-induced liver injury in mice demonstrates that wound closure precedes hepatocyte proliferation. 4-D intravital imaging of APAP-induced mouse liver injury identifies motile hepatocytes at the edge of the necrotic area, enabling collective migration of the hepatocyte sheet to effect wound closure. Depletion of hepatocyte ANXA2 expression reduces HGF-induced human and mouse hepatocyte migration in vitro, and abrogates necrotic wound closure following APAP-induced mouse liver injury. Taken together, our work dissects unanticipated aspects of liver regeneration, demonstrating an uncoupling of wound closure and hepatocyte proliferation and uncovering a novel migratory hepatocyte subpopulation which mediates wound closure following liver injury. Therapies designed to promote rapid reconstitution of normal hepatic microarchitecture and reparation of the gut-liver barrier may open up new areas of therapeutic discovery in regenerative medicine.

cell biology↗