Biology subjects

Taing, L.

Publications and source records attributed to Taing, L..

6 recordsLinked to original sources

bioRxiv2026

mTORC1 supports progression toward activation competence in quiescent adult neural stem cells

Neural stem cells (NSCs) sustain lifelong neurogenesis through the tight regulation of quiescence, self-renewal and differentiation. Quiescent NSCs (qNSCs) exist in distinct substates, ranging from deep to shallow quiescence, yet the mechanisms governing these transitions remain unclear. In long-term self-renewing NSCs of the adult zebrafish pallium, we show that mTORC1 activity is specifically enriched during a prolonged quiescence phase in which NSCs acquire activation competence. Functional perturbations, analyzed in situ and using single-cell RNA sequencing, reveal that mTORC1 regulates cell progression during this phase, concomitantly ensuring the correct tempo for NSC transition towards activation and the preservation of stemness. These findings challenge the classical view of mTORC1 as a simple regulator of proliferation and identify it as a key regulator of NSC quiescence heterogeneity and dynamics under physiological conditions. By coordinating stemness maintenance with activation competence, mTORC1 emerges as a central player balancing long-term NSC preservation with neurogenic output in the adult brain.

cell biology↗

bioRxiv2026

Topological Regulation of the Mammalian Genome by Positive DNA Supercoiling

DNA supercoiling is a fundamental aspect of genome topology characterizing all DNA transactions. While negative supercoiling has been extensively characterized, positive supercoiling remains poorly understood. Using a quantitative GapR profiling system, we establish comprehensive maps of positive supercoiling across interphase and mitosis. We show that positive super-coils accumulate not only at gene ends but prominently at promoters, enhancers, insulators and loop anchors, where they are resolved by Topoisomerases. Biochemical and functional assays reveal the main sources of positive torsion: transcription generates genic supercoils, while R-loops and Cohesin drive accumulation at regulatory elements, topologically associating domains and their boundaries. During mitotic chromosomal compaction, Condensins establish a global wave of positive supercoiling that largely homogenizes the genome, yet promoters with rapid post-mitotic reactivation retain elevated torsion and R-loops. These findings establish positive DNA supercoiling as a form of topological memory that links DNA mechanics to transcriptional control, genome architecture and epigenetic inheritance.

molecular biology↗

bioRxiv2023

Operant training for highly palatable food alters translating mRNA in nucleus accumbens D2 neurons and reveals a modulatory role of Neurochondrin

BACKGROUNDHighly palatable food triggers behavioral alterations reminiscent of those induced by addictive drugs. These effects involve the reward system and dopamine neurons, which modulate neurons in the nucleus accumbens (NAc). The molecular mechanisms underlying the effects of highly palatable food on feeding behavior are poorly understood. METHODSWe studied the effects of 2-week operant conditioning of mice with standard or isocaloric highly palatable food. We investigated the behavioral effects and dendritic spine modifications in the NAc. We compared the translating mRNA in NAc neurons identified by the type of dopamine receptors they express, depending on the type of food and training. We tested the consequences of invalidation of an abundant downregulated gene, Ncdn (Neurochondrin). RESULTSOperant conditioning for highly palatable food increases motivation for food even in well-fed mice. In control mice, free access to regular or highly palatable food results in increased weight as compared to regular food only. Highly palatable food increases spine density in the NAc. In animals trained for highly palatable food, translating mRNAs are modified in NAc dopamine D2-receptor-expressing neurons, mostly corresponding to striatal projection neurons, but not in those expressing D1-receptors. Knock-out of Ncdn, an abundant down-regulated gene, opposes the conditioning-induced changes in satiety-sensitive feeding behavior and apparent motivation for highly palatable food, suggesting down-regulation may be a compensatory mechanism. CONCLUSIONSOur results emphasize the importance of mRNA alterations D2 striatal projection neurons in the NAc in the behavioral consequences of highly palatable food conditioning and suggest a modulatory contribution of Ncdn downregulation.

neuroscience↗

bioRxiv2021

CHIPS: A Snakemake pipeline for quality control and reproducible processing of chromatin profiling data

MotivationThe chromatin profile measured by ATAC-seq, ChIP-seq, or DNase-seq experiments can identify genomic regions critical in regulating gene expression and provide insights on biological processes such as diseases and development. However, quality control and processing chromatin profiling data involve many steps, and different bioinformatics tools are used at each step. It can be challenging to manage the analysis. ResultsWe developed a Snakemake pipeline called CHIPS (CHromatin enrichment Processor) to streamline the processing of ChIP-seq, ATAC-seq, and DNase-seq data. The pipeline supports single- and paired-end data and is flexible to start with FASTQ or BAM files. It includes basic steps such as read trimming, mapping, and peak calling. In addition, it calculates quality control metrics such as contamination profiles, PCR bottleneck coefficient, the fraction of reads in peaks, percentage of peaks overlapping with the union of public DNaseI hypersensitivity sites, and conservation profile of the peaks. For downstream analysis, it carries out peak annotations, motif finding, and regulatory potential calculation for all genes. The pipeline ensures that the processing is robust and reproducible. AvailabilityCHIPS is available at https://github.com/liulab-dfci/CHIPS

bioinformatics↗

bioRxiv2020

CoBRA: Containerized Bioinformatics workflow for Reproducible ChIP/ATAC-seq Analysis - from differential peak calling to pathway analysis

ChIP-seq and ATAC-seq have become essential technologies used as effective methods of measuring protein-DNA interactions and chromatin accessibility. However, there is a need for a scalable and reproducible pipeline that incorporates correct normalization between samples, adjustment of copy number variations, and integration of new downstream analysis tools. Here we present CoBRA, a modularized computational workflow which quantifies ChIP and ATAC-seq peak regions and performs unsupervised and supervised analysis. CoBRA provides a comprehensive state-of-the-art ChIP and ATAC-seq analysis pipeline that is usable by scientists with limited computational experience. This enables researchers to gain rapid insight into protein-DNA interactions and chromatin accessibility through sample clustering, differential peak calling, motif enrichment, comparison of sites to a reference DB and pathway analysis. Code availability: https://bitbucket.org/cfce/cobra

bioinformatics↗

bioRxiv2020

Translational profiling of mouse dopaminoceptive neurons reveals a role of PGE2 in dorsal striatum

Forebrain dopaminoceptive neurons play a key role in movement, action selection, motivation, and working memory. Their activity is dysregulated in addiction, Parkinsons disease and other conditions. To characterize the diverse dopamine target neuronal populations, we compare translating mRNAs in neurons of dorsal striatum and nucleus accumbens expressing D1 or D2 dopamine receptor and prefrontal cortex expressing D1 receptor. We identify D1/D2 and striatal dorso-ventral differences in the translational and splicing landscapes, which establish the characteristics of dopaminoceptive neurons. Expression differences and network analyses identify novel transcription factors with presumptive roles in these differences. Prostaglandin E2 appears as a candidate upstream regulator in the dorsal striatum, a hypothesis supported by converging functional evidence indicating its role in enhancing D2 dopamine receptor action. Our study provides powerful resources for characterizing dopamine target neurons, new information about striatal gene expression patterns, and reveals the unforeseen role of prostaglandin E2 in the dorsal striatum.

neuroscience↗