A5022647005- Hearing, Cochlea, Tinnitus, Genetics
- Hearing Loss and Rehabilitation
- Acoustic Wave Phenomena Research
- Cancer-related molecular mechanisms research
- Plant Molecular Biology Research
- Marine animal studies overview
- Single-cell and spatial transcriptomics
- Developmental Biology and Gene Regulation
- Ear Surgery and Otitis Media
- Neurobiology and Insect Physiology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Interconnection Networks and Systems
- Congenital heart defects research
- Ion Channels and Receptors
- Animal Vocal Communication and Behavior
- Connexins and lens biology
- CRISPR and Genetic Engineering
- Vestibular and auditory disorders
- Genetics, Aging, and Longevity in Model Organisms
- Fibroblast Growth Factor Research
- Chemical and Physical Studies
- RNA and protein synthesis mechanisms
- Machine Learning in Bioinformatics
- Cancer Cells and Metastasis
- Advanced Optical Network Technologies
Center for Excellence in Brain Science and Intelligence Technology
2017-2025
Chinese Academy of Sciences
2015-2025
University of Chinese Academy of Sciences
2017-2025
Shanghai Center for Brain Science and Brain-Inspired Technology
2019-2025
Jiangxi University of Science and Technology
2024
Fujian Medical University
2024
Institute of Automation
2015-2024
Institute of Genetics and Developmental Biology
2021-2024
West China Hospital of Sichuan University
2014-2024
University of Sheffield
2023-2024
Inner ear hair cells are specialized sensory essential for auditory function. Previous studies have shown that the epithelium is postmitotic, but it harbors can behave as progenitor in vitro, including ability to form new cells. Lgr5 , a Wnt target gene, marks distinct supporting cell types neonatal cochlea. Here, we tested hypothesis + Wnt-responsive precursor In contrast their quiescent vivo behavior, isolated by flow cytometry from EGFP-CreERT2/+ mice proliferated and formed clonal...
Loss of cochlear hair cells in mammals is currently believed to be permanent, resulting hearing impairment that affects more than 10% the population. Here, we developed two genetic strategies ablate neonatal mouse vivo. Both Pou4f3DTR/+ and Atoh1-CreER™; ROSA26DTA/+ alleles allowed selective inducible cell ablation. After loss was induced at birth, observed spontaneous regeneration cells. Fate-mapping experiments demonstrated neighboring supporting acquired a fate, which increased basal...
Unlike nonmammalian vertebrates, mammals cannot convert inner ear cochlear supporting cells (SCs) into sensory hair (HCs) after damage, thus causing permanent deafness. Here, we achieved in vivo conversion of two SC subtypes, pillar (PCs) and Deiters' (DCs), HCs by inducing targeted expression Atoh1 at neonatal juvenile ages using novel mouse models. The only occurred ∼10% PCs DCs with ectopic started reactivation endogenous followed 11 HC synaptic markers, a process that took approximately...
Neural stem cells show age-dependent developmental potentials, as evidenced by their production of distinct neuron types at different times. Drosophila neuroblasts produce long, stereotyped lineages neurons. We searched for factors that could regulate neural temporal fate RNA-sequencing lineage-specific various found two RNA-binding proteins, IGF-II mRNA-binding protein (Imp) and Syncrip (Syp), display opposing high-to-low low-to-high gradients with dynamics. Imp Syp promote early late...
Mammalian cochlear outer hair cells (OHCs) are essential for hearing. Severe hearing impairment follows OHC degeneration. Previous attempts at regenerating new OHCs from supporting (SCs) have been unsuccessful, notably lacking expression of the key motor protein, Prestin. Thus, regeneration Prestin+ represents a barrier to restore auditory function in vivo. Here, we reported successful vivo conversion adult mouse SCs into OHC-like through concurrent induction two transcriptional factors...
The cochlea harbors two types of sound receptors, outer hair cells (OHCs) and inner (IHCs). OHCs transdifferentiate into IHCs in Insm1 mutants, Ikzf2-deficient mice are dysfunctional maintain partial IHC gene expression. potentially acts as a positive but indirect regulator Ikzf2, considering that is expressed earlier than Ikzf2 primarily functions transcriptional repressor. However, direct evidence this possibility lacking. Here, we report the following results: first, overexpression leads...
Regeneration of auditory hair cells (HCs) is a promising approach to restore hearing. Recent studies have demonstrated that induced pluripotent stem cells/embryonic or supporting (SCs) adjacent HCs can be converted adopt the HC fate. However, little known about whether new are characteristic outer inner HCs. Here, we showed in vivo conversion 2 subtypes SCs, border (IBs) and phalangeal (IPhs), (IHC) This was achieved by ectopically activating Atoh1, transcription factor necessary for fate,...
Distance metric learning (DML) is an important technique to improve similarity search in content-based image retrieval. Despite being studied extensively, most existing DML approaches typically adopt a single-modal framework that learns the distance on either single feature type or combined space where multiple types of features are simply concatenated. Such methods suffer from some critical limitations: (i) may significantly dominate others task due diverse representations; and (ii)...
Inner ear cochlear spiral ganglion neurons (SGNs) transmit sound information to the brainstem. Recent single cell RNA-Seq studies have revealed heterogeneities within SGNs. Nonetheless, much remains unknown about transcriptome of SGNs, especially which genes are specifically expressed in To address these questions, we needed a deeper and broader gene coverage than that previous studies. We performed bulk on mouse SGNs at five ages, two reference types (hair cells glia). Their comparison...
Atoh1 is essential for the development of both outer hair cells (OHCs) and inner (IHCs) in mammalian cochlea. Whereas Ikzf2 necessary OHC development, key gene required IHC remains unknown. We found that deletion Tbx2 neonatal IHCs led to their transdifferentiation into OHCs by repressing 26.7% genes inducing 56.3% genes, including Ikzf2. More importantly, persistent expression coupled with transient effectively reprogrammed non-sensory supporting new expressing functional marker vGlut3. The...
Cochlear hair cells (HCs) in the inner ear are responsible for sound detection. For HC fate specification, master transcription factor Atoh1 is both necessary and sufficient. expression dynamic tightly regulated during development, but cis -regulatory elements mediating this regulation remain unresolved. Unexpectedly, we found that deleting only recognized enhancer, defined here as Eh1, failed to impair development. By using assay transposase-accessible chromatin with high-throughput...
Inner ear vestibular and spiral ganglion neurons (VGNs SGNs) are known to play pivotal roles in balance control sound detection. However, the molecular mechanisms underlying otic neurogenesis at early embryonic ages have remained unclear. Here, we use single-cell RNA sequencing reveal transcriptomes of mouse tissues three ages, day 9.5 (E9.5), E11.5, E13.5, covering proliferating undifferentiated neuroblasts differentiating VGNs SGNs. We validate high quality our studies by using multiple...
Abstract Sonic hedgehog (Shh) signaling plays important roles in the formation of auditory epithelium. However, little is known about detailed expression pattern Shh and cell sources from which secreted. By analyzing CreEGFP/+ mice, we found that was first expressed all cochlear spiral ganglion neurons by embryonic day 13.5, after its gradually decreased base to apex. postnatal 0, it not detected any neurons. Genetic fate mapping results also confirmed exclusively surrounding glia cells. The...
A brain consists of numerous distinct neurons arising from a limited number progenitors, called neuroblasts in Drosophila. Each neuroblast produces specific neuronal lineage. To unravel the transcriptional networks that underlie development lineages, we marked and isolated lineage-specific for RNA sequencing. We labeled particular throughout neurogenesis by activating conditional driver lineages using various intersection strategies. The targeted were efficiently recovered custom-built...
ABSTRACT In vivo genetic mutation has become a powerful tool for dissecting gene function; however, multi-gene interaction and the compensatory mechanisms involved can make findings from single mutations, at best difficult to interpret, and, worst, misleading. Hence, it is necessary establish an efficient way disrupt multiple genes simultaneously. CRISPR/Cas9-mediated base editing disrupts function by converting protein-coding sequence into stop codon; this referred as CRISPR-stop. Its...
The molecular and cellular organization of the primate cerebellum remains poorly characterized. We obtained single-cell spatial transcriptomic atlases macaque, marmoset, mouse cerebella identified primate-specific cell subtypes, including Purkinje cells molecular-layer interneurons, that show different expression glutamate ionotropic receptor Delta type subunit 2 ( GRID2 ) gene. Distinct gene profiles were found in anterior, posterior, vestibular regions all species, whereas region-selective...
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...
Citrullination, the deimination of peptidylarginine residues into peptidylcitrulline catalyzed by deiminase (PADs), has been confirmed as a unique form posttranslational modification proteins. Among five isoforms PADs, PAD2 is main PAD enzyme expressed in central nervous system (CNS). Previous studies reported that citrullinated proteins was increasingly associated with neurological disorders such Alzheimer's disease, prion disease and Multiple Sclerosis. However, physiological role CNS are...