Biology subjects

Tse, Y. C.

Publications and source records attributed to Tse, Y. C..

4 recordsLinked to original sources

bioRxiv2026

Prophase Chromosomes Relocalizes to Nuclear Periphery for Protection in Depletion of Nucleoporin NPP-3/NUP205 Through the Spindle Assembly Checkpoint Activity, Centromere-Kinetochore Proteins and BAF-1-LEM-2

The nuclear envelope (NE) mediates transport between nucleus and cytoplasm in eukaryotic cells and protects genetic materials against cytoplasmic enzymes. Nuclear pore complexes (NPCs) regulate chromosome architecture, genome integrity, gene transcription, and cell division. In Caenorhabditis elegans embryos, depletion of NPP-3/NUP205 causes NE rupture, premature chromosome condensation, and relocalization of condensed chromosomes to the nuclear periphery, similar to responses during anoxia and quiescence. This chromosomal relocalization depends on the spindle assembly checkpoint (SAC), inner kinetochore proteins, and partially on the NE rupture repair proteins BAF-1 and LEM-2. NPP-3 depletion prolongs prophase and prometaphase, as mediated by SAC proteins MDF-1 and MDF-2. Additionally, NPP-3 depletion alters MDF-1 localization, removing it from NE and increasing its nuclear accumulation, while reducing import of kinetochore components such as KNL-1, BUB-1, and HCP-1. In 20-30 cell-stage embryos, MDF-1 foci are observed on peripheral chromosomes during prophase. Both MDF-1 and MDF-2 accumulate on chromosomes during prometaphase. The increased incidence of lagging chromosomes, DNA damage, and micronuclei upon NPP-3 and MDF-1 depletion, suggesting that peripheral chromosome localization may serve as a protective mechanism against DNA damage. These findings shed light into cellular responses to NE rupture, with potential implications for laminopathies and cancers involving nuclear envelope defects.

cell biology↗

bioRxiv2024

Uncertainty gates redundancy in reward integration in prefrontal-cortical and ventral-hippocampal nucleus accumbens inputs to tune engagement

The NAc, a highly integrative brain region controlling motivated behavior, is thought to receive distinct information from various glutamatergic inputs yet strong evidence of functional specialization of inputs is lacking. While circuit neuroscience commonly seeks specific functions for specific circuits, redundancy can be highly adaptive and is a critical motif in circuit organization. Using dual-site fiber photometry in an operant reward task, we simultaneously recorded from two NAc glutamatergic afferents to assess circuit specialization. We identify a common neural motif that integrates reward history in medial prefrontal cortex (mPFC) and ventral hippocampus (vHip) inputs to NAc. Then, by systematically degrading task complexity, dissociating reward from choice and action, we identify key circuit-specificity in the behavioral conditions that recruit encoding. While mPFC-NAc invariantly encodes reward, vHip-NAc encoding is uniquely anchored to loss. Ultimately, using optogenetic stimulation we demonstrate that both inputs co-operatively modulate task engagement. We illustrate how similar encoding, with differential gating by behavioral state, supports state-sensitive tuning of reward-motivated behavior.

neuroscience↗

bioRxiv2022

Sexually dimorphic neural encoding of threat discrimination in nucleus accumbens afferents drives suppression of reward behavior

Learning to predict threat is essential but equally important yet often overlooked is learning about the absence of threat. Interrogating neural activity in two nucleus accumbens afferents in male and female mice during aversive and neutral cues reveals sex-specific encoding of cue discrimination and cuemediated suppression of reward behavior. Sexual dimorphisms in neural bases of threat discrimination may reflect sex differences in behavioral strategy relevant to differential psychiatric risk.

neuroscience↗

bioRxiv2019

Amplification-free Library Preparation Improves Quality of Hi-C Analysis

PCR amplification of Hi-C libraries introduces unusable duplicates and results in a biased representation of chromatin interactions. We present a simplified, fast, and economically efficient Hi-C library preparation procedure that generates sufficient non-amplified ligation products for deep sequencing from 30 million Drosophila cells. Comprehensive analysis of the resulting data indicates that amplification-free Hi-C preserves higher complexity of chromatin interaction and lowers sequencing depth dramatically for the same number of unique paired reads. For human cells which has a large genome, this method recovers an amount of ligated fragments enough for direct high-throughput sequencing without amplification on as low as 250 thousand of cells. Comparison with published in situ Hi-C on millions of human cells reveals that amplification introduces distance-dependent amplification bias, which results in increasing background noise level against genomic distance. With amplification bias avoided, our method may produce a chromatin interaction network more faithfully reflecting the real three-dimensional genomic architecture.

genomics↗