A cochlear progenitor pool influences patterning of the mammalian sensory epithelium via MYBL2 DOI Creative Commons
Caryl A. Young, Emily K. Burt, Vidhya Munnamalai

et al.

Development, Journal Year: 2024, Volume and Issue: 151(17)

Published: Sept. 1, 2024

ABSTRACT During embryonic development, Wnt signaling influences both proliferation and sensory formation in the cochlea. How this dual nature of is coordinated unknown. In study, we define a novel role for Wnt-regulated gene, Mybl2, which was already known to be important proliferation, determining size patterning epithelium murine Using quantitative spatial analysis approach analyzing Mybl2 loss-of-function, show that promoted inner sulcus domain but limited by influencing their adjoining boundary position via Jag1 regulation during development. loss-of-function simultaneously decreased increased domain, resulting wider with ectopic hair cell late stages. These data suggest progenitor cells determine pattern MYBL2.

Language: Английский

Casz1 is required for both inner hair cell fate stabilization and outer hair cell survival DOI
Yuwei Sun,

Minhui Ren,

Yu Zhang

et al.

Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Cochlear inner hair cells (IHCs) and outer (OHCs) require different transcription factors for their cell fate stabilization survival, suggesting separate mechanisms are involved. Here, we found that the factor Casz1 was crucial early IHC consolidation OHC survival during mouse development. Loss of resulted in transdifferentiation IHCs into OHCs, without affecting production. However, long-term compromised mutant mice. In addition, Gata3 down-regulated -deleted overexpressing partially rescued properties, numbers, hearing Thus, plays critical roles could potentially provide a lead therapies aimed at regenerating both OHCs.

Language: Английский

Citations

1
Comparative Transcriptional Analysis of Long Noncoding RNAs in Oxidative Stress and Inflammation Induced by Potassium Permanganate and Lipopolysaccharide in Rat Uterine Tissues DOI Creative Commons
Talha Umar,

Huili Feng,

Wen Feng

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 251 - 251

Published: Feb. 21, 2025

Potassium permanganate (KMnO4) is a commercially available antiseptic used in bovine intrauterine lavage to manage postpartum infections. Lipopolysaccharides (LPS) are well-studied for their ability induce inflammation and oxidative stress. While KMnO4 known cause significant irritation, stress, toxicity uterine tissues, its transcriptional impact potential inducing similar molecular damage as LPS have not been fully explored. In this study, we induced stress the tissues of Sprague-Dawley (SD) rats using compared profiles with those treated LPS. We focused on differential expression long noncoding RNAs (lncRNAs) messenger (mRNAs) related toxicity, inflammation. RNA sequencing revealed 1125 differentially expressed mRNAs KMnO4-treated group 989 LPS-treated group. Additionally, 1649 lncRNAs were 1383 Gene ontology (GO) KEGG enrichment analyses showed that 78 pathways significantly enriched group, while 80 50 shared between two. This study offers critical insights into associated exposure similarities LPS-induced damage.

Language: Английский

Citations

1
Spatiotemporal dynamics of inner ear sensory and non-sensory cells revealed by single-cell transcriptomics DOI Creative Commons
Taha A. Jan, Yasmin Eltawil,

Angela H. Ling

et al.

Cell Reports, Journal Year: 2021, Volume and Issue: 36(2), P. 109358 - 109358

Published: July 1, 2021

The utricle is a vestibular sensory organ that requires mechanosensitive hair cells to detect linear acceleration. In neonatal mice, new are derived from non-sensory supporting cells, yet cell type diversity and mechanisms of addition remain poorly characterized. Here, we perform computational analyses on single-cell transcriptomes categorize types resolve 14 individual subtypes. Along the periphery epithelium, uncover distinct groups transitional epithelial marked by Islr, Cnmd, Enpep expression. By reconstructing de novo trajectories gene dynamics, show as expands, Islr+ exhibit dynamic proliferative phase generate followed coordinated differentiation into cells. Taken together, our study reveals sequential process which contribute growth postnatal mouse epithelium.

Language: Английский

Citations

54
Organ of Corti size is governed by Yap/Tead-mediated progenitor self-renewal DOI Open Access
Ksenia Gnedeva, Xizi Wang, Melissa M. McGovern

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(24), P. 13552 - 13561

Published: June 1, 2020

Precise control of organ growth and patterning is executed through a balanced regulation progenitor self-renewal differentiation. In the auditory sensory epithelium—the Corti—progenitor cells exit cell cycle in coordinated wave between E12.5 E14.5 before initiation receptor differentiation, making it unique system for studying molecular mechanisms controlling switch proliferation Here we identify Yap/Tead complex as key regulator gene network Corti cells. We show that Tead transcription factors bind directly to putative regulatory elements many stemness- cycle-related genes. also coactivator protein, Yap, degraded specifically Sox2-positive domain cochlear duct, resulting down-regulation targets. Further, conditional loss Yap inner ear results formation significantly smaller vestibular epithelia, while overexpression constitutively active version , Yap5SA sufficient prevent prolong tissue growth. viral delivery postnatal epithelia vivo drives reentry after hair loss. Taken together, these data highlight role factor maintaining progenitors during development, suggest new strategies induce regeneration.

Language: Английский

Citations

43
Identifying Treatments for Taste and Smell Disorders: Gaps and Opportunities DOI Creative Commons
Joel D. Mainland, Linda A. Barlow, Steven D. Munger

et al.

Chemical Senses, Journal Year: 2020, Volume and Issue: 45(7), P. 493 - 502

Published: June 5, 2020

The chemical senses of taste and smell play a vital role in conveying information about ourselves our environment. Tastes smells can warn against danger also contribute to the daily enjoyment food, friends family, surroundings. Over 12% US population is estimated experience (chemosensory) dysfunction. Yet, despite this high prevalence, long-term, effective treatments for these disorders have been largely elusive. Clinical successes other sensory systems, including hearing vision, led new hope developments treatment chemosensory disorders. To accelerate cures, we convened "Identifying Treatments Taste Smell Disorders" conference, bringing together basic translational scientists, health care professionals, patients identify gaps current understanding dysfunction next steps broad-based research strategy. Their suggestions high-yield were focused 3 areas: increasing awareness capacity (e.g., patient advocacy), developing enhancing clinical measures smell, supporting avenues into cellular therapeutic approaches human cell lines, stem cells, gene therapy approaches). These long-term strategies specific immediate priorities that focus on expanding responses cells valuable assays document development, regeneration, function. Addressing high-priority areas should development novel

Language: Английский

Citations

43
Maresin 1 Activates LGR6 to Alleviate Neuroinflammation via the CREB/JMJD3/IRF4 Pathway in a Rat Model of Subarachnoid Hemorrhage DOI
Zhenyan Li, Wen Yuan, Xian‐Wen Yang

et al.

Neuroscience, Journal Year: 2024, Volume and Issue: 542, P. 21 - 32

Published: Feb. 8, 2024

Language: Английский

Citations

4
Foxm1 promotes differentiation of neural progenitors in the zebrafish inner ear. DOI

Maria Ali,

James Warren Kutlowski,

Jorden N Holland

et al.

Developmental Biology, Journal Year: 2025, Volume and Issue: 520, P. 21 - 30

Published: Jan. 4, 2025

Language: Английский

Citations

0
Crosstalk Signaling Between the Epithelial and Non-Epithelial Compartments of the Mouse Inner Ear DOI Creative Commons
Abel P. David, Sushobhan Biswas,

Macey P. Soltis

et al.

Journal of the Association for Research in Otolaryngology, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Abstract Purpose The otolith organs of the inner ear consist utricle and saccule that detect linear acceleration. These rely on mechanosensitive hair cells for transduction signals to central nervous system. In murine utricle, about half are born during first postnatal week. Here, we wanted explore role interaction non-epithelial mesenchymal with sensory epithelium provide a resource auditory neurosciences community. Methods We utilized full-length Smart-seq2 single-cell RNA sequencing at days 4 6 along host computational methods infer interactions between epithelial compartments mouse utricle. validated these findings using combination immunohistochemistry quantitative multiplex in situ hybridization. Results report diverse cell–cell crosstalk among 12 annotated cell populations ( n = 955 cells) developing neonatal including cellular signaling. dominant signal senders period. Epithelial signaling, as well quantitatively shown through TGFβ pleiotrophin pathways. Conclusion This study highlights dynamic process vestibular organ development relies not only cells, but also spatial different groups. further data-rich

Language: Английский

Citations

0
PROX1 Controls Cellular Patterning, Innervation and Differentiation in the Mouse Organ of Corti DOI Creative Commons

Shubham Kale,

Dimitri Traenkner,

Ellison J. Goodrich

et al.

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

Published: April 16, 2025

Abstract The organ of Corti is divided into functional compartments responsible for hearing or cochlear amplification. A medial compartment containing inner hair cells innervated by Type I spiral ganglion neurons and a lateral outer II neurons. Supporting also differ, with pillar Deiters’ developing specialized cellular structures to support cell electromotility. We bred Corti-restricted Prox1 conditional knockout mice study development because PROX1 the first transcription factor expressed strictly in supporting cells. In absence , numbers increased without corresponding changes cells, they appear incompletely differentiated based on morphological criteria. Outer number was not impacted but innervation disrupted many afferent turning incorrectly towards apex. RNAseq revealed no gene expression that could account phenotype. Therefore, we propose promotes differentiation organization has secondary effects required specification.

Language: Английский

Citations

0
Wnts regulate planar cell polarity via heterotrimeric G protein and PI3K signaling DOI Creative Commons
André Landin Malt, Arielle Hogan, Connor D. Smith

et al.

The Journal of Cell Biology, Journal Year: 2020, Volume and Issue: 219(10)

Published: Aug. 17, 2020

In the mammalian cochlea, planar cell polarity (PCP) pathway aligns hair orientation along plane of sensory epithelium. Concurrently, multiple intrinsic (referred to as iPCP) modules mediate polarization apical cytoskeleton, including kinocilium and V-shaped bundle essential for mechanotransduction. How PCP iPCP are coordinated during development roles Wnt ligands in this process remain unresolved. Here we show that genetic blockade secretion cochlear epithelium resulted a shortened duct misoriented misshapen bundles. Mechanistically, Wnts stimulate Gi activity by regulating localization Daple, guanine nucleotide exchange factor (GEF) Gαi. turn, Gβγ complex signals through phosphoinositide 3-kinase (PI3K) regulate positioning asymmetric localizations subset core proteins, thereby coordinating iPCP. Thus, our results identify putative Wnt/heterotrimeric G protein/PI3K regulation.

Language: Английский

Citations

21