Genes, Journal Year: 2023, Volume and Issue: 14(2), P. 380 - 380
Published: Jan. 31, 2023
The precise control of neural crest stem cell delamination, migration and differentiation ensures proper craniofacial head development. Sox2 shapes the ontogeny cranial to ensure precision flow in developing head. Here, we review how orchestrates signals that these complex developmental processes.
Language: Английский
Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)
Published: May 25, 2021
Abstract Hippo signaling is an evolutionarily conserved pathway that restricts growth and regeneration predominantly by suppressing the activity of transcriptional coactivator Yap. Using a high-throughput phenotypic screen, we identified potent non-toxic activator In vitro kinase assays show compound acts as ATP-competitive inhibitor Lats kinases—the core enzymes in signaling. The substance prevents Yap phosphorylation induces proliferation supporting cells murine inner ear, cardiomyocytes, human Müller glia retinal organoids. RNA sequencing indicates reversibly activates expression targets: upon withdrawal, subset supporting-cell progeny exits cell cycle upregulates genes characteristic sensory hair cells. Our results suggest pharmacological inhibition kinases may promote initial stages proliferative cells, process thought to be permanently suppressed adult mammalian ear.
Language: Английский
Citations
134
Science Translational Medicine, Journal Year: 2021, Volume and Issue: 13(600)
Published: June 30, 2021
Gene therapy–mediated disruption of Hippo signaling results in tissue renewal and improved function pigs after myocardial infarction.
Language: Английский
Citations
106
Development, Journal Year: 2021, Volume and Issue: 148(12)
Published: June 15, 2021
ABSTRACT The balance between stem cell potency and lineage specification entails the integration of both extrinsic intrinsic cues, which ultimately influence gene expression through activity transcription factors. One example this is provided by Hippo signalling pathway, plays a central role in regulating organ size during development. pathway mediated transcriptional co-factors Yes-associated protein (YAP) co-activator with PDZ-binding motif (TAZ), interact TEA domain (TEAD) proteins to regulate expression. Although roles YAP TAZ have been intensively studied, played TEAD are less well understood. Recent studies begun address this, revealing that TEADs progenitor self-renewal differentiation throughout various stages Furthermore, it becoming apparent other biology. This Primer provides an overview development, focusing on their as within developmental, homeostatic disease contexts.
Language: Английский
Citations
79
Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(2)
Published: Jan. 19, 2022
Abstract The Hippo/Yes-associated protein (YAP) signaling pathway has been shown to be able maintain organ size and homeostasis by regulating cell proliferation, differentiation, apoptosis. abuse of aminoglycosides is one the main causes sensorineural hearing loss (SSNHL). However, role Hippo/YAP in cochlear hair (HC) damage protection auditory field still unclear. In this study, we used YAP agonist XMU-MP-1 (XMU) inhibitor Verteporfin (VP) regulate vitro. We showed that overexpression reduced neomycin-induced HC loss, while downregulated expression increased vulnerability after neomycin exposure next found activation inhibited C-Abl-mediated apoptosis, which led loss. Many previous studies have reported level reactive oxygen species (ROS) significantly HCs exposure. our also decreased ROS accumulation, downregulation accumulation. summary, results demonstrate plays an important reducing injury maintaining function aminoglycoside could protect against inhibiting apoptosis decreasing suggesting a novel therapeutic target for aminoglycosides-induced clinic.
Language: Английский
Citations
47
Science Advances, Journal Year: 2022, Volume and Issue: 8(6)
Published: Feb. 11, 2022
Hair cell (HC) loss within the inner ear cochlea is a leading cause for deafness in humans. Before onset of hearing, immature supporting cells (SCs) neonatal mice have some limited capacity HC regeneration. Here, we show that organoid culture, transient activation progenitor-specific RNA binding protein LIN28B and Activin antagonist follistatin (FST) enhances regenerative competence maturing/mature cochlear SCs by reprogramming them into progenitor-like cells. Transcriptome profiling mechanistic studies reveal drives SC reprogramming, while FST required to counterbalance hyperactivation transforming growth factor–β–type signaling LIN28B. Last, coactivation spontaneous regeneration may be part an endogenous repair mechanism primes These findings indicate dedifferentiation critical identify as main regulators.
Language: Английский
Citations
40
Cell Death and Differentiation, Journal Year: 2020, Volume and Issue: 28(1), P. 24 - 34
Published: Dec. 14, 2020
Abstract While inner ear disorders are common, our ability to intervene and recover their sensory function is limited. In vitro models of the ear, like organoid system, could aid in identifying new regenerative drugs gene therapies. Here, we provide a perspective on status guidance how improve applicability translational research. We highlight generation cell types from pluripotent stem cells as particularly promising focus Several exciting recent studies have shown developmental signaling cues embryonic fetal development can be mimicked differentiate into “inner organoids” containing otic progenitor cells, hair neurons. However, current differentiation protocols knowledge general, bias toward epithelia ear. propose that more holistic view needed better model vitro. Moving forward, attention should made broader diversity neuroglial mesenchymal they interact space or time during development. With improved control epithelial, neuroglial, fate specification, organoids would truly recapitulate neurosensory dysfunction. conclude by discussing single-cell atlases developing technical innovations will critical tools advance platforms for future pre-clinical applications.
Language: Английский
Citations
56
Development, Journal Year: 2024, Volume and Issue: 151(2)
Published: Jan. 15, 2024
ABSTRACT Cell shape is a powerful readout of cell state, fate and function. We describe custom workflow to perform semi-automated, 3D nucleus segmentation, spherical harmonics principal components analysis distill nuclear variation into discrete biologically meaningful parameters. apply these methods analyze in the neuromast cells zebrafish lateral line system, finding that shapes vary with location identity. The distinction between hair support accounted for much variation, which allowed us train classifiers predict identity from features. Using transgenic markers subpopulations, we found subtypes had different each other. To investigate how loss type altered distributions, examined atoh1a mutants lack cells. mutant neuromasts lacked phenotype associated cells, but did not exhibit mutant-specific shape. Our results demonstrate utility using features characterize, compare classify living developing organism.
Language: Английский
Citations
5
Stem Cell Reports, Journal Year: 2022, Volume and Issue: 18(1), P. 319 - 336
Published: Dec. 29, 2022
Functional cochlear hair cells (HCs) innervated by spiral ganglion neurons (SGNs) are essential for hearing, whereas robust models that recapitulate the peripheral auditory circuity still lacking. Here, we developed organoids with functional in a staging three-dimensional (3D) co-culture system initially reprogramming progenitor (CPCs) increased proliferative potency could be long-term expanded, then stepwise inducing differentiation of HCs, as well outgrowth neurites from SGNs. The function HCs and synapses within was confirmed series morphological electrophysiological evaluations. Single-cell mRNA sequencing revealed trajectories CPCs toward major cell types dynamic gene expression during organoid HC development, which resembled pattern native HCs. We established first time, provides platform deciphering mechanisms sensorineural hearing loss.
Language: Английский
Citations
20
Pharmacology Research & Perspectives, Journal Year: 2022, Volume and Issue: 10(3)
Published: May 22, 2022
Abstract Despite a prevalence greater than cancer or diabetes, there are no currently approved drugs for the treatment of hearing loss. Research over past two decades has led to vastly improved understanding cellular and molecular mechanisms in cochlea that lead deficits advent novel strategies combat them. Combined with innovative methods enable local drug delivery inner ear, these insights have paved way promising therapies now under clinical investigation. In this review, we will outline renaissance cochlear biology development, focusing on noise, age‐related, chemotherapy‐induced dysfunction.
Language: Английский
Citations
19
International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 6994 - 6994
Published: April 10, 2023
Sensorineural hearing loss is the most prevalent sensory deficit in humans. Most cases of are due to degeneration key structures pathway cochlea, such as hair cells, primary auditory neurons, and their synaptic connection cells. Different cell-based strategies replace damaged inner ear neurosensory tissue aiming at restoration regeneration or functional recovery currently subject intensive research. these treatment approaches require experimental vitro models that rely on a fine understanding earliest morphogenetic steps underlie vivo development since its initial induction from common otic–epibranchial territory. This knowledge will be applied various proposed cell replacement either address feasibility identify novel therapeutic options for sensorineural loss. In this review, we describe how epibranchial placode can recapitulated by focusing cellular transformations occur converted thickening surface ectoderm next hindbrain known otic an otocyst embedded head mesenchyme. Finally, highlight events towards progenitors derivatives.
Language: Английский
Citations
12