Wnt signalling facilitates neuronal differentiation of cochlear Frizzled10-positive cells in mouse cochlea via glypican 6 modulation

Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 27, 2025

Degeneration of cochlear spiral ganglion neurons (SGNs) leads to irreversible sensorineural hearing loss (SNHL), as SGNs lack regenerative capacity. Although glial cells (GCs) have some neuronal differentiation potential, their specific identities remain unclear. This study identifies a distinct subpopulation, Frizzled10 positive (FZD10+) cells, an important type GC responsible for in mouse cochlea. FZD10 + can differentiate into various SGN subtypes vivo, adhering natural proportions. Wnt signaling enhances the ability function neural progenitors and increases excitability FZD10-derived neurons. Single-cell RNA sequencing analysis characterizes differentiating cell populations, while crosstalk network multiple pathways target genes influenced by that contribute progenitors. Pseudotime maps trajectory from proliferated GCs Further experiments indicate glypican 6 (GPC6) may regulate this lineage, GPC6 deficiency diminishes effects on synapse formation. These findings suggest critical role derived provide insights mechanisms potentially involved process.

Язык: Английский

Musculoskeletal Organoids: An Emerging Toolkit for Establishing Personalized Models of Musculoskeletal Disorders and Developing Regenerative Therapies

Acta Biomaterialia, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Musculoskeletal (MSK) conditions are the primary cause of physical disability globally. These disorders physically and mentally debilitating severely impact patients' quality life. As median age world's population increases, there has been an intensifying urgency developing efficacious therapies for various orthopaedic conditions. Furthermore, highly heterogeneous nature MSK calls a personalized approach to studying disease mechanisms regenerative treatments. Organoids have emerged as advanced generating functional tissue/organ mimics in vitro, which hold promise regeneration, modeling, therapeutic development. Herein, we review preparation, characterization, application organoids. We highlight potential patient-specific organoids development medicine discuss challenges opportunities future STATEMENT OF SIGNIFICANCE: Despite decades research, translation research into clinical applications remains limited, partially attributed our inadequate understanding mechanisms. To advance development, critical needs models with higher relevance predictive power. Additionally, engineered constructs that closely mimic structural features native tissues desirable. promising meet above requirements. unleash full necessitates comprehensive their categories, construction, functions, applications, challenges. This aims fulfill this crucial need, aiming accelerate organoid platforms benefit millions patients afflicted

Язык: Английский