Biology subjects

Hwang, Y.-C.

Publications and source records attributed to Hwang, Y.-C..

6 recordsLinked to original sources

bioRxiv2025

Mesenchymal Stem Cell-Mediated Intercellular Communication: Mapping the Interactome for Skeletal Muscle Homeostasis and Regeneration

Mesenchymal stem cells (MSCs) support tissue homeostasis and regeneration, yet their molecular signals remain largely enigmatic. In skeletal muscle (SkM), MSCs, known as fibroadipogenic progenitors (FAPs), are essential for maintenance and repair, orchestrating these processes through intricate cellular communication networks. Given the critical role of SkM in lifelong health and longevity, FAP signaling has drawn significant interest as a potential therapeutic target and a model for MSC interactions. However, deciphering FAP-derived regulatory signals remains challenging due to their pleiotropic complexity. Here, we employ a systems-based approach to construct a comprehensive FAP interactome in both homeostatic and regenerating SkM. By integrating unique single-cell RNA sequencing atlases with advanced computational analyses, we identify putative FAP-mediated signaling pathways and validate their biological relevance through FAP depletion experiments, assessing disruptions in key pathways. This approach reveals novel signaling networks across diverse SkM cell populations, corroborates key FAP interactions from recent studies, and provides a valuable dataset for modeling MSC interactions and their roles in SkM homeostasis and regeneration.

cell biology↗

bioRxiv2021

Towards a Comprehensive Variation Benchmark for Challenging Medically-Relevant Autosomal Genes

The repetitive nature and complexity of multiple medically important genes make them intractable to accurate analysis, despite the maturity of short-read sequencing, resulting in a gap in clinical applications of genome sequencing. The Genome in a Bottle Consortium has provided benchmark variant sets, but these excluded some medically relevant genes due to their repetitiveness or polymorphic complexity. In this study, we characterize 273 of these 395 challenging autosomal genes that have multiple implications for medical sequencing. This extended, curated benchmark reports over 17,000 SNVs, 3,600 INDELs, and 200 SVs each for GRCh37 and GRCh38 across HG002. We show that false duplications in either GRCh37 or GRCh38 result in reference-specific, missed variants for short- and long-read technologies in medically important genes including CBS, CRYAA, and KCNE1. Our proposed solution improves variant recall in these genes from 8% to 100%. This benchmark will significantly improve the comprehensive characterization of these medically relevant genes and guide new method development.

genomics↗

bioRxiv2020

Open-source mapping and variant calling for large-scale NGS data from original base-quality scores

AO_SCPLOWBSTRACTC_SCPLOWStandardized genome informatics protocols minimize reprocessing costs and facilitate harmonization across studies if implemented in a transparent, accessible and reproducible manner. Here we define the OQFE protocol, a lossless read-mapping protocol that retains key features of existing NGS standard methods. We demonstrate that variants can be called directly from NovaSeq OQFE data without the need for base quality score recalibration and describe a large-scale variant calling protocol for OQFE data. The OQFE protocol is open-source and a containerized implementation is provided.

bioinformatics↗

bioRxiv2019

HIPPIE2: a method for fine-scale identification of physically interacting chromatin regions

Most regulatory chromatin interactions are mediated by various transcription factors (TFs) and involve physically-interacting elements such as enhancers, insulators, or promoters. To map these elements and interactions, we developed HIPPIE2 which analyzes raw reads from high-throughput chromosome conformation (Hi-C) experiments to identify fine-scale physically-interacting regions (PIRs). Unlike standard genome binning approaches (e.g., 10K-1Mbp bins), HIPPIE2 dynamically calls physical locations of PIRs with better precision and higher resolution based on the pattern of restriction events and relative locations of interacting sites inferred from the sequencing readout.\n\nWe applied HIPPIE2 to in situ Hi-C datasets across 6 human cell lines (GM12878, IMR90, K562, HMEC, HUVEC, NHEK) with matched ENCODE and Roadmap functional genomic data. HIPPIE2 detected 1,042,738 distinct PIRs across cell lines, with high resolution (average PIR length of 1,006bps) and high reproducibility (92.3% in GM12878 replicates). 32.8% of PIRs were shared among cell lines. PIRs are enriched for epigenetic marks (H3K27ac, H3K4me1) and open chromatin, suggesting active regulatory roles. HIPPIE2 identified 2.8M significant intrachromosomal PIR-PIR interactions, 27.2% of which were enriched for TF binding sites. 50,608 interactions were enhancer-promoter interactions and were enriched for 33 TFs (31 in enhancers/29 in promoters), several of which are known to mediate DNA looping/long-distance regulation. 29 TFs were enriched in >1 cell line and 4 were cell line-specific. These findings demonstrate that the dynamic approach used in HIPPIE2 (https://bitbucket.com/wanglab-upenn/HIPPIE2) characterizes PIR-PIR interactions with high resolution and reproducibility.

bioinformatics↗

bioRxiv2019

A doublecortin-domain protein of Toxoplasma and its orthologues bind to and modify the structure and organization of tubulin polymers

TgDCX is a doublecortin-domain protein associated with the conoid fibers, a set of strongly curved non-tubular tubulin-polymers in Toxoplasma. TgDCX deletion impairs conoid structure and parasite invasion. TgDCX contains two tubulin-binding domains: a partial P25-alpha and the DCX/doublecortin domain. Orthologues are found in apicomplexans and their free-living relatives Chromera and Vitrella. We report that isolated TgDCX-containing conoid fibers retain their pronounced curvature, but loss of TgDCX destabilizes the fibers. We crystallized and determined the 3D-structure of the DCX-domain, which is similar to those of human doublecortin and well-conserved among TgDCX orthologues. However, the orthologues vary widely in targeting to the conoid in Toxoplasma and in modulating microtubule organization in Xenopus cells. Several orthologues bind to microtubules in Xenopus cells, but only TgDCX generates short, strongly curved microtubule arcs. EM analysis shows microtubules decorated with TgDCX bundled into rafts, often bordered on one edge by a "C"-shaped incomplete tube. A Chromera orthologue closely mimics TgDCX targeting in Toxoplasma and binds to microtubules in Xenopus cells, but does not generate arcs or "C"-shaped tubes, and fails to rescue the defects of the TgDCX-knockout parasite. These observations suggest that species-specific features of TgDCX enable it to generate strongly curved tubulin-polymers to support efficient host-cell invasion.

cell biology↗

bioRxiv2017

Stability and function of a putative microtubule organizing center in the human parasite Toxoplasma gondii

The organization of the microtubule cytoskeleton is dictated by microtubule nucleators or organizing centers. Toxoplasma gondii, an important human parasite, has an array of 22 regularly spaced cortical microtubules stemming from a hypothesized organizing center, the apical polar ring. Here, we examine the functions of the apical polar ring by characterizing two of its components, KinesinA and APR1, and discovered that its putative role in templating can be separated from its mechanical stability. Parasites that lack both KinesinA and APR1 ({Delta}kinesinA{Delta}apr1) are capable of generating 22 cortical microtubules. However, the apical polar ring is fragmented in live{Delta} kinesinA{Delta}apr1 parasites, and is undetectable by electron microscopy after detergent extraction. Disintegration of the apical polar ring results in the detachment of groups of microtubules from the apical end of the parasite. These structural defects are linked to a diminished ability of the parasite to move and to invade host cells, as well as decreased secretion of effectors important for these processes. Together, the findings demonstrate the importance of the structural integrity of the apical polar ring and the microtubule array in the Toxoplasma lytic cycle, which is responsible for massive tissue destruction in acute toxoplasmosis.

cell biology↗