Long-Read RNA-sequencing reveals transcript-specific regulation in human-derived cortical neurons DOI Creative Commons
Jishu Xu, Michaela Hörner, Elena Buena‐Atienza

et al.

Published: Nov. 11, 2024

Abstract Long-read RNA sequencing has transformed transcriptome analysis by enabling comprehensive mapping of full-length transcripts, providing an unprecedented resolution transcript diversity, alternative splicing, and transcript-specific regulation. In this study, we employed nanopore long-read to profile the transcriptomes human fibroblasts, induced pluripotent stem cells, cell-derived cortical neurons, identifying extensive diversity with 15,072 transcripts in 13,048 12,759 cells. Our analyses uncovered 35,519 differential expression events 5,135 usage events, underscoring complexity transcriptomic regulation across these cell types. Importantly, integrating analyses, gained deeper insights into dynamics that are not captured gene-level alone. Notably, highlighted changes disease-relevant genes such as APP, KIF2A , BSCL2 associated Alzheimer’s disease, neuronal migration disorders, degenerative axonopathies, respectively. This added emphasizes significance transcript- level variations often remain hidden traditional gene analyses. Overall, our work provides a framework for understanding both specialized types, which can be used investigate disease states. Additionally, study underscores utility advancing neurodevelopmental neurodegenerative diseases, paving way therapeutic targets.

Language: Английский

Direct Current Stimulation (DCS) Modulates Lipid Metabolism and Intercellular Vesicular Trafficking in SHSY‐5Y Cell Line: Implications for Parkinson's Disease DOI Creative Commons
Marco Piccoli,

Libero M. Barbato,

Natale Maiorana

et al.

Journal of Neurochemistry, Journal Year: 2025, Volume and Issue: 169(2)

Published: Feb. 1, 2025

ABSTRACT The modulation of the brain's electrical activity for therapeutic purposes has recently gained attention, supported by promising results obtained through non‐invasive application transcranial direct current stimulation (tDCS) in treatment neurodegenerative and neurological diseases. To optimize efficacy, it is crucial to investigate cellular molecular effects tDCS. This will help identify important biomarkers, predict patient's response develop personalized treatments. In this study, we applied (DCS) a neural cell line, using mild currents over short periods time (0.5 mA, 20 min), with 24‐h intervals. We observed that DCS induced changes lipidome, transient after single (lasting 24 h) more significant, long‐lasting (up 72 repeated cycles. cells, multiple modulated structural membrane lipids (PE, PS, PI), downregulated glycerol ether‐linked fatty acids pro‐inflammatory (ceramides lyso‐glycerophospholipids) ( p ≤ 0.005). Multiple sessions altered transcriptional decreasing expression inflammatory cytokines (TNF‐α, 0.05; IL‐1β, 0.01), while increasing neuroprotective factors such as heme oxygenase‐1 0.0001) brain‐derived neurotrophic factor 0.05), well proteins involved vesicular transport (SNARE, sorting nexins seipin α‐synuclein; 0.05). addition, enhanced release extracellular vesicles, stimulations significantly exosomes threefold. conclusion, induces metabolic limited phenotypic effects, applications induce broader deeper lipid species. may lead neuroplasticity‐focussed profile, potentially supporting tDCS at level patients.. image

Language: Английский

Citations

1
Role of lipid droplets in neurodegenerative diseases: From pathogenesis to therapeutics DOI Creative Commons

Yubing Kang,

Yee Jie Yeap, Jing Yang

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 165, P. 105867 - 105867

Published: Aug. 28, 2024

Neurodegenerative diseases (NDDs) are a series of disorders characterized by the progressive loss specific neurons, leading to cognitive and locomotor impairment. NDDs affect millions patients worldwide but lack effective treatments. Dysregulation lipids, particularly accumulation lipid droplets (LDs), is strongly implicated in pathogenesis NDDs. How LDs contribute occurrence development NDDs, their potential as therapeutic targets remain be addressed. In present review, we first introduce processes formation, transportation degradation. We then highlight how contributes cell type-specific manner. Moreover, discuss currently available methods for detecting elaborate on LDs-based strategies Lastly, identify gaps that need filled better leverage LD-based theranostics other diseases. hope this review could shed light role facilitate novel

Language: Английский

Citations

6
Seipin Deficiency Impairs Motor Coordination in Mice by Compromising Spinal Cord Myelination DOI
Hong Chen, Wenru Wang, Wenli Cui

et al.

NeuroMolecular Medicine, Journal Year: 2025, Volume and Issue: 27(1)

Published: Jan. 27, 2025

Language: Английский

Citations

0
A lipid droplet-targeted NIR fluorescent probe for viscosity detection in Parkinson's disease DOI

Sufang Ma,

Leyan Li,

Pinyu Wan

et al.

Sensors and Actuators B Chemical, Journal Year: 2024, Volume and Issue: 420, P. 136441 - 136441

Published: Aug. 13, 2024

Language: Английский

Citations

2
Seipin Regulates Caveolin-1 Trafficking and Organelle Crosstalk DOI
Maxime Carpentier, Mohyeddine Omrane,

Rola Shaaban

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Abstract Caveolin-1 (CAV1), the main structural component of caveolae, is essential in various biological processes, including mechanotransduction, lipid metabolism, and endocytosis 1–4 . Deregulation CAV1 dynamics linked to pathologies, cellular senescence, cancer, insulin resistance, lipodystrophy 5–9 However, mechanisms regulating trafficking function remain poorly understood. Here, we show that seipin, a crucial droplet (LD) biogenesis factor 10 , modulates trafficking. Deletion seipin resulted accumulation saturated lipids, leading ceramide sphingomyelin overproduction, which disrupted membrane order trans-Golgi network (TGN). In deficiency, location plasma (PM) was impaired, reducing caveolae. Instead, accumulated TGN late endosome compartments, fused with LDs delivered protein. wild-type (WT) cells, this process minimal but significantly enhanced by treatment palmitate, ceramide, or Stearoyl-CoA desaturase-1 (SCD1) inhibition. Conversely, seipin-deficient inhibiting Fatty Acid Synthase (FASN) overexpressing SCD1 restored localization PM reduced its LDs. Our findings reveal controls funneling palmitate toward glycerolipids synthesis storage versus conversion ceramides ER. This balance protein controlling order. Therefore, our study identifies as critical regulator trafficking, organelle homeostasis. These shed light on processes convergent pathophysiological associated defects contribute metabolic disorders, resistance lipodystrophies 11–14

Language: Английский

Citations

1
Long-Read RNA-sequencing reveals transcript-specific regulation in human-derived cortical neurons DOI Creative Commons
Jishu Xu, Michaela Hörner, Elena Buena‐Atienza

et al.

Published: Nov. 11, 2024

Abstract Long-read RNA sequencing has transformed transcriptome analysis by enabling comprehensive mapping of full-length transcripts, providing an unprecedented resolution transcript diversity, alternative splicing, and transcript-specific regulation. In this study, we employed nanopore long-read to profile the transcriptomes human fibroblasts, induced pluripotent stem cells, cell-derived cortical neurons, identifying extensive diversity with 15,072 transcripts in 13,048 12,759 cells. Our analyses uncovered 35,519 differential expression events 5,135 usage events, underscoring complexity transcriptomic regulation across these cell types. Importantly, integrating analyses, gained deeper insights into dynamics that are not captured gene-level alone. Notably, highlighted changes disease-relevant genes such as APP, KIF2A , BSCL2 associated Alzheimer’s disease, neuronal migration disorders, degenerative axonopathies, respectively. This added emphasizes significance transcript- level variations often remain hidden traditional gene analyses. Overall, our work provides a framework for understanding both specialized types, which can be used investigate disease states. Additionally, study underscores utility advancing neurodevelopmental neurodegenerative diseases, paving way therapeutic targets.

Language: Английский

Citations

0