Biology subjects

Tseng, C.-Y.

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

6 recordsLinked to original sources

bioRxiv2026

NECAP antagonizes light-induced Rhodopsin-1 internalization to promote photoreceptor homeostasis

AP-2 is a key mediator of clathrin-mediated endocytosis (CME) that internalizes cargo from the plasma membrane. NECAP proteins physically bind phosphorylated AP-2 during CME, but their roles during endocytosis remain unresolved, with conflicting reports about their function. Here, we report that Drosophila NECAP is dispensable for development, but antagonizes light-dependent Rhodopsin-1 (Rh1) internalization, a process that occurs through AP-2-mediated endocytosis. Specifically, loss of Drosophila NECAP causes excessive light-dependent Rh1 internalization and an age-related retinal degeneration that can be rescued by photoreceptor-specific expression of a wild-type transgenic NECAP. A Drosophila NECAP mutant transgene, equivalent to a canine NECAP1 variant associated with retinal atrophy, failed to rescue the NECAP loss-of-function phenotype in the eye. Furthermore, overexpression of wild-type NECAP suppressed massive Rh1 internalization in a distinct Drosophila model of light-dependent Rh1 endocytosis and retinal degeneration. These results establish NECAP as a negative regulator of light-dependent Rh1 internalization essential for photoreceptor survival.

cell biology↗

bioRxiv2025

Age-related declines in niche self-renewal factors controls testis aging and spermatogonial stem cell competition through Hairless, Imp, and Chinmo

Aging is associated with progressive tissue decline and shifts in stem cell clonality. The role of niche signals in driving these processes remains poorly understood. Using the Drosophila testis, we identify a regulatory axis in which age-related decline of niche signals (BMPs) lead to upregulation of the co-repressor Hairless, which downregulates the RNA-binding protein Imp in aged germline stem cells (GSCs). Reduced Imp causes loss of Chinmo, a key factor in GSC aging and competition. Reduced Chinmo causes ectopic Perlecan secretion which accumulates in the testis lumen and causes GSC loss. Aging of the testis is reversed by increasing BMPs in the niche, or by overexpressing Imp or depleting Hairless in GSCs. Furthermore, GSC clones with reduced Imp or increased Hairless are more competitive, expelling wild-type neighbors and monopolizing the niche. Thus, BMPs regulate testicular niche aging through the Hairless-Imp-Chinmo axis and "winning" GSCs usurp these aging mechanisms. HighlightsO_LIAged niche cells produce less BMPs, resulting in more Hairless (H) in aged GSCs C_LIO_LIElevated H represses Imp, resulting in less Chinmo and in ectopic ECM secretion C_LIO_LIAging is prevented by higher BMP in niche cells, or by higher Imp or lower H in GSCs C_LIO_LIGSCs with low Imp or high H exploit these aging mechanisms to colonize the GSC pool C_LI

genetics↗

bioRxiv2024

MOS4-Associated Complex subunits 3A and 3B modulate FLM splicing to repress photoperiod-dependent floral transition

Plants adjust their flowering time by integrating environmental cues through complex regulatory networks. RNA splicing plays a crucial role in modulating gene expression in response to flowering signals. The MOS4-associated complex (MAC), consisting of the evolutionarily conserved E3 ubiquitin ligases MAC3A and MAC3B, is pivotal in splicing regulation. However, their involvement in floral transition remained unclear. This study observed that mac3a/mac3b mutants flowered significantly earlier under short-day (SD) conditions, a phenotype absent under long-day (LD) conditions. This early flowering correlated with upregulation of FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1) compared to wild-type plants. Transcriptomic analysis revealed alterations in transcript levels and splicing profiles of key floral regulators across different flowering pathways. Further investigation identified the thermosensory flowering regulator FLOWERING LOCUS M (FLM) as being influenced by MAC3A and MAC3B. Subsequently, we found that MAC3A and MAC3B exhibited higher expression and were associated with FLM transcripts to modulate their splicing in SD. This study elucidates how the MAC complex, through RNA splicing regulation, integrates environmental signals to modulate flowering, unveiling a new layer of complexity in flowering pathways crosstalk under non-inductive photoperiods.

plant biology↗

bioRxiv2023

High-throughput, label-free detection of DNA origami in single-cell suspensions using origamiFISH-Flow

Structural DNA nanotechnology enables custom fabrication of nanoscale devices and promises diverse biological applications. However, the effects of design on DNA nanostructure (DN)-cell interactions in vitro and in vivo are not yet well-characterized. origamiFISH is a recently developed technique for imaging DNs in cells and tissues. Compared to the use of fluorescent tags, origamiFISH offers label-free and structure-agnostic detection of DNs with significantly improved sensitivity. Here, we extend the origamiFISH technique to quantifying DNs in single-cell suspensions, including nonadherent cells such as subsets of immune cells, via readout by flow cytometry. This method, referred to as origamiFISH-Flow, is high-throughput (e.g., 10,000 cells per second) and compatible with immunostaining for concurrent cell-type and -state characterization. We demonstrate that origamiFISH-Flow enhances signal-to-noise ratio by up to 20-fold compared to dye labeling approaches, leading to the capture of >25-fold more DN+ cells at low, single-picomolar DN uptake concentrations. We additionally show the use of origamiFISH-Flow to profile cell-type and shape-specific DN uptake patterns across cell lines and splenocytes and quantify in vivo DN accumulation in lymphoid organs. Together, origamiFISH-Flow offers a new tool to interrogate DN interactions with cells and tissues, while providing insights for tailoring their designs in bio-applications.

bioengineering↗

bioRxiv2022

Canonical Wnt signaling promotes formation of somatic permeability barrier for proper germ cell differentiation

Morphogen-mediated signaling is critical for proper organ development and stem cell function, and well-characterized mechanisms spatiotemporally limit the expression of ligands, receptors, and ligand-binding cell-surface glypicans. Here, we show that in the developing Drosophila ovary, canonical Wnt signaling promotes the formation of somatic escort cells (ECs) and their protrusions, which establish a physical permeability barrier to define morphogen territories for proper germ cell differentiation. The protrusions shield germ cells from Dpp and Wingless morphogens produced by the germline stem cell (GSC) niche and normally only received by GSCs. Genetic disruption of EC protrusions allows GSC progeny to also receive Dpp and Wingless, which subsequently disrupt germ cell differentiation. Our results reveal a role for canonical Wnt signaling in specifying the ovarian somatic cells necessary for germ cell differentiation. Additionally, we demonstrate the morphogen-limiting function of this physical permeability barrier, which may be a common mechanism in other organs across species.

developmental biology↗

bioRxiv2021

Daily transient coating of the intestine leads to weight loss and improved glucose tolerance

The worsening obesity epidemic has driven a parallel increase in incidence of type-2 diabetes (T2D) found in 13% of the adult US population. Roux-en-Y gastric bypass surgery (RYGB) is the golden standard surgical treatment for obesity-related T2D. However, over 70% of T2D patient do not meet the NIH criteria for surgery, and many that do, are reluctant to consider such an invasive intervention. Mechanisms behind the antidiabetic effect of RYGB are not clearly understood, but isolation of proximal bowel from nutrient exposure plays a critical role. In this study, we tested the impact of daily administration of an oral gut coating agent, LuCI (Luminal Coating of the Intestine), in controlling weight and insulin resistance. LuCI is not systemically absorbed and provides a transient coating of the proximal intestines and excludes the coated bowel from nutrient contact, thus mimicking the effects of RYGB. We demonstrate that LuCI results in weight loss and improved insulin sensitivity in a rat DIO model. LuCI also appears to replicate hormonal changes seen after RYGB, by increasing post-prandial GLP-1 and GIP levels. LuCI has the potential to replicate the metabolic benefit of surgery and be a novel therapeutic strategy for obesity associated T2D.

bioengineering↗