Single-cell transcriptomic profiling of the zebrafish inner ear reveals molecularly distinct hair cell and supporting cell subtypes

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Jan. 4, 2023

A major cause of human deafness and vestibular dysfunction is permanent loss the mechanosensory hair cells inner ear. In non-mammalian vertebrates such as zebrafish, regeneration missing can occur throughout life. While a comparative approach has potential to reveal basis differential regenerative ability, degree which ears fish mammals share common supporting cell types remains unresolved. Here, we perform single-cell RNA sequencing zebrafish ear at embryonic through adult stages catalog diversity non-sensory cells. We identify putative progenitor population for cells, well distinct in maculae versus cristae. The differ from those described lateral line system, distributed organ most studies have been conducted. maculae, two subtypes that gene expression with mammalian striolar or extrastriolar situ hybridization reveals these occupy spatial domains within three macular organs, utricle, saccule, lagena, consistent reported electrophysiological properties domains. These findings suggest primitive specialization spatially likely arose last ancestor mammals. similarities type composition between validate relevant model understanding ear-specific function regeneration.

Language: Английский

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Hallmarks of regeneration

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(9), P. 1244 - 1261

Published: Aug. 19, 2024

Language: Английский

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Vestibular physiology and function in zebrafish

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: April 18, 2023

The vestibular system of the inner ear provides information about head motion and spatial orientation relative to gravity ensure gaze stability, balance, postural control. Zebrafish, like humans, have five sensory patches per that serve as peripheral organs, with addition lagena macula neglecta. zebrafish can be easily studied due its accessible location, transparent tissue larval fish, early development behaviors. Thus, are an excellent model for studying development, physiology, function system. Recent work has made great strides elucidate neural circuitry in tracing transmission from receptors periphery central computational circuits driving reflexes. Here we highlight recent illuminates functional organization epithelia, innervating first-order afferent neurons, second-order neuronal targets hindbrain. Using a combination genetic, anatomical, electrophysiological, optical techniques, these studies probed roles signals fish gaze, postural, swimming We discuss remaining questions tractable model.

Language: Английский

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A screen for regeneration-associated silencer regulatory elements in zebrafish

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(5), P. 676 - 691.e5

Published: Jan. 29, 2024

Language: Английский

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Cardiac enhancers: Gateway to the regulatory mechanisms of heart regeneration

Seminars in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 170, P. 103610 - 103610

Published: April 10, 2025

Language: Английский

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No trout about it: behavioural and transcriptional effects of long-term noise exposure in brook trout (Salvelinus fontinalis)

Canadian Journal of Fisheries and Aquatic Sciences, Journal Year: 2025, Volume and Issue: 82, P. 1 - 16

Published: Jan. 1, 2025

Exposure to acute noise sources can lead negative behavioural outcomes and fitness deficits in fishes, but it is unknown whether fish habituate chronic exposures. As underwater increases globally, understanding how long-term exposures affect behavioural, morphological, transcriptional measures of stress critical. We tested responses captive brook trout ( Salvelinus fontinalis) immediately after exposure a 2 weeks exposure. Behavioural tests quantified movements before, during, sound presentation, with morphological changes assessed through ears whole brains samples, respectively. Pre-control pre-experimental exhibited increased swimming distance velocity, the 2-week exposure, post-experimental showed no response while post-control group remained responsive. Post-experimental significant differences transcription levels genes involved neuroplastic, appetite, relative other groups. Together these results suggest that may appear unresponsive via metrics anthropogenic noises they still show at level possible effects.

Language: Английский

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Stem Cells in Regenerative Medicine: Unlocking Therapeutic Potential Through Stem Cell Therapy, 3D Bioprinting, Gene Editing, and Drug Discovery

Biomedical Engineering Advances, Journal Year: 2025, Volume and Issue: unknown, P. 100172 - 100172

Published: May 1, 2025

Language: Английский

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Common and specific gene regulatory programs in zebrafish caudal fin regeneration at single-cell resolution

Genome Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Following amputation, zebrafish regenerate their injured caudal fin through lineage-restricted reprogramming. Although previous studies have charted various genetic and epigenetic dimensions of this process, the intricate gene regulatory programs shared by, or unique to, different regenerating cell types remain underinvestigated. Here, we mapped landscape regeneration by applying paired snRNA-seq snATAC-seq on uninjured fins. This map delineates dynamics predominant populations at multiple stages regeneration. We observe a marked increase in accessibility chromatin regions associated with regenerative developmental processes 1 dpa, followed gradual closure across major later stages. pattern is distinct from that transcriptomic dynamics, which characterized several waves upregulation downregulation. identified vivo validated cell-type-specific position-specific regeneration-responsive enhancers constructed networks type stage. Our single-cell resolution provides new insights into mechanisms serves as valuable resource for community.

Language: Английский

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The Notch ligand Jagged1 plays a dual role in cochlear hair cell regeneration

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

ABSTRACT Hair cells (HCs) within the inner ear cochlea are specialized mechanoreceptors required for hearing. Cochlear HCs not regenerated in mammals, and their loss is a leading cause of deafness humans. supporting (SCs) newborn mice have capacity to regenerate HCs, but persistent Notch signaling, presumably activated by SC-specific ligand Jagged1 (JAG1), prevents SCs from converting into HCs. Here, employing an organoid platform, we show that while JAG1 participates HC-fate repression, JAG1’s primary function preserve “progenitor-like characteristics” cochlear SCs. Transcriptomic mechanistic studies reveal JAG1/Notch signaling maintains expression progenitor metabolic genes sustains pro-growth pathways, including PI3K-Akt-mTOR mediated Notch1 Notch2. Finally, stimulation with JAG1-Fc peptide enhances HC-forming undergoing maturation explants vivo .

Language: Английский

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Transdifferentiation is temporally uncoupled from progenitor pool expansion during hair cell regeneration in the zebrafish inner ear

Development, Journal Year: 2024, Volume and Issue: 151(15)

Published: July 24, 2024

ABSTRACT Death of mechanosensory hair cells in the inner ear is a common cause auditory and vestibular impairment mammals, which have limited ability to regrow these after damage. In contrast, non-mammalian vertebrates, including zebrafish, can robustly regenerate severe organ The zebrafish provides an understudied model system for understanding cell regeneration organs that are highly conserved with their mammalian counterparts. Here, we quantitatively examine addition during growth larval ear. We used genetically encoded ablation method induce death observed gradual correct spatial patterning over 2-week period following ablation. Supporting cells, surround source new divide response ablation, expanding possible progenitor pool. parallel, nascent arise from direct transdifferentiation pool temporally uncoupled supporting division. These findings reveal previously unrecognized mechanism implications how may be encouraged

Language: Английский

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