ScRNA-seq of mouse cochlea organoid cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE326100 | GEO | 2026/04/07
REPOSITORIES: GEO
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Project description:Purpose and Methods: Cochlear sensory hair cells (HCs) are essential for our sense of hearing. They are embedded in the organ of Corti that lacks regenerative capacity, which is a major cause of hearing loss. However, some neonatal non-sensory cells in the organ of Corti display a limited regenerative ability. We used fluorescence-activated cell sorting (FACS) to isolate different cochlear cell types from postnatal day 2 (P2) mice to assess the individual cell groups’ potential to grow organoids and to generate new HCs. Single-cell RNAseq validated the composition of the cell types in the sorted cell groups. Results and Conclusions: The greater epithelial ridge (GER), a transient tissue that only exists in the neonatal inner ear, harbored the most potent organoid-forming cells. GER-derived organoids expanded into large colonies when cultured adherently and gave rise to new hair cell marker-expressing cells in a sensory epithelia-resembling organization. The organoid forming ability of GER cells was synergistically enhanced when they were cultured at increasing density. The synergistic effect relied on direct cell-to-cell contact rather than released soluble factors.
2020-12-29 | GSE162308 | GEO
Project description:The hair cells of the cochlea play a decisive role in the process of hearing damage and recovery, yet knowledge of their regeneration process is still limited. Greater epithelial ridge (GER) cells, a type of cell present during cochlear development that has the characteristics of a precursor sensory cell, disappear at the time of maturation of hearing development. Its development and evolution remain mysterious for many years. Here, we performed single-cell RNA sequencing to profile the gene expression landscapes of rats' cochlear duct from P1, P7, and P14 and identified eight major subtypes of GER cells. Furthermore, single-cell trajectory analysis for GER cells and hair cells indicated that among the different subtypes of GER, four subtypes had transient cell proliferation after birth and could transdifferentiate into inner and outer hair cells, and two of them mainly transdifferentiated into inner hair cells. The other two subtypes eventually transdifferentiate into outer hair cells. Our study lays the groundwork for elucidating the mechanisms of the key regulatory genes and signaling pathways in the trans-differentiation of GER cell subtypes into hair cells and provides potential clues to understand hair cell regeneration.
2022-01-29 | GSE195702 | GEO
Project description:Greater epithelial ridge cells, a transient neonatal cell group in the cochlear duct, which plays a crucial role in the functional maturation of hair cell, structural development of tectorial membrane, and refinement of audio localization before hearing. Greater epithelial ridge cells are methodologically homogeneous, while whether different cell subtypes are existence in this intriguing region and the degeneration mechanism during postnatal cochlear development are poorly understood. In the present study, single-cell RNA sequencing was performed on the cochlear duct of postnatal rats at day 1 (P1) and day 7 (P7) to identify subsets of greater epithelial ridge cell and progression. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to examine genes enriched biological processes in these clusters. We identified a total of 26 clusters at P1 and P7 rats and found that the cell number of five cell clusters decreased significantly, while four clusters had similar gene expression patterns and biological properties. The genes of these four cell populations were mainly enriched in Ribosome and P13K-Akt signal pathway. Among them, Rps16, Rpsa, Col4a2, Col6a2, Ctsk, and Jun are particularly interesting as their expression might contribute to the greater epithelial ridge cells degeneration. In conclusion, our study provides an important reference resource of greater epithelial ridge cells landscape and mechanism insights for further understanding greater epithelial ridge cells degeneration during postnatal rat cochlear development
2021-09-02 | GSE170810 | GEO
Project description:Cochlear supporting cells are critical for proper hearing function and regeneration of hair cells, which are responsible for perceiving sound in the inner ear. In the neonatal mouse cochlea, when supporting cells are ablated, they can regenerate through progenitor cells in the cochlea. Here, we show through single cell RNA sequencing and in vivo fate mapping, that upon supporting cell ablation in the neonatal cochlea, inner phalangeal cells regenerate through two independent mechanisms; one which requires proliferation and the other by which transdifferentiation (i.e. regeneration without mitotic division) of cochlear progenitor cells occurs. These dual mechanisms are spatially distinct where transdifferentiation occurs in all three turns of the cochlea, while proliferation-induced regeneration occurs exclusively in the apical and middle turns. Inhibiting proliferation using aphidicolin, slightly decreased the number of regenerated IPhCs in the apex middle turns, but not the base, after damage. We also observed a medial to lateral transition in the compartmentalization of the GER after supporting cell damage, suggesting de-differentiation of these domains. Overall, our study reveals GER cells as supporting cell progenitors that undergo dual mechanisms of regeneration (mitotic and non-mitotic). Additionally, we uncover transcriptomic changes after supporting cell damage in the neonatal mouse cochlea that could be used as gene targets in therapies for hearing loss.
2026-01-12 | GSE291228 | GEO
Project description:Purpose - To determine transcriptomic variations in the mouse cochlea in response to three different transcription factor overexpression conditions and no induction control and to determine transcriptomic and accessible chromatin variations in the mouse cochlea between postnatal day 1 (P1) and postnatal day 8 (P8) stages of development. Methods - SC RNA seq performed on FACS enriched cells obtained from experimental animals (Sox9CreER; Rosa26A/GA/GAP/+; Rosa26 tdtomato). Same samples at two timepoints 1 week (P8) and 2 week (P15) ages. scMultiome ATAC + Gene Expression (10x Genomics) experiments on enzymatically dissociated and unenriched cochlear nuclei from wildtype mice in a mixed background of CD1 and FVB/NJ, and C57BL/6. Samples were collected at P1 and P8. Gene expression data was used to annotate clusters. Chromatin accessibility determined by ATAC was compared between P1 and P8 stages. Results - The SC RNA seq highlighted differential transcriptomic changes between the two ages and the three overexpression conditions. Hair cell loci become less epigenetically accessible in supporting cells and GER cells between P1 and P8. Conclusions - Our study highlights the variability in transcriptomic response to three transcription factor combination mediated reprogramming cues at two different ages. The SC RNA seq confirmed a variety of our biological observations with regard to the hair cell reprogramming process in the mouse cochlea. We also demonstrate variability in chromatin accessibility between P1 and P8, which may explain why GER and supporting cells of the cochlea become more resistant to transcription factor reprogramming into hair cells during the first postnatal week.
2022-08-01 | GSE182202 | GEO
Project description:Organoids from KPC pancreatic tumor tissue was treated with growth medium or conditional medium of mast cells treated with WT or BAG6 KO EVS of Pan02.
2024-12-31 | E-MTAB-13570 | biostudies-arrayexpress
Project description:We sought to directly measure the molecular response in the cochlear immune cells following noise exposure.
2021-08-19 | GSE167078 | GEO
Project description:The mouse cochlear sensory epithelium proteome has been characterized using FASP combined with GELFrEE and off-line SCX- and WAX-based methods follwed by nano LC-MS/MS. In addition, we utilzed single digestion and double digestion approaches using LysC and trypsin endoproteases. MS data files were processed with MaxQuant (Version 1.2.2.5, Max Planck Institute) and peak list files were searched by MASCOT search engine against the UniProt mouse database containing both forward and reversed protein sequences and common contaminants such as keratin. The initial parent and fragment ion maximum precursors were set to 6 ppm and 0.5 Da, respectively. The search included a fixed modification of carbamidomethyl of cysteine and variable modifications of oxidation of methionine and protein N-terminal acetylation. The minimum peptide length to be considered for identification was 6 amino acids.
2013-06-28 | PXD000231 | Pride
Project description:This data set is intended as a public resource documenting the identity of roughly 10,000 genes that are abundantly expressed in the mouse cochlea. The data have many uses, including for making comparisons with proteomics studies, and for comparisons of expression profiles with other mouse strains and with other species. The CBA/CaJ strain was chosen because of its lack of known vulnerabilities to premature cochlear degeneration or to extreme reactions to cochlear stresses. It may therefore be considered a “normal” mouse. No experimental manipulations were done on the mice of this study. Contamination of the results by genes expressed in the surrounding petrous bone and from those in blood cells was minimized. Keywords: normal controls
2008-11-01 | GSE13421 | GEO
Project description:The homeobox transcription factor Prox1 is critical for organogenesis including brain, retina, liver and pancreas and lymphatic system. Prox1 is transiently expressed in mouse cochlear hair cells (HCs) and supporting cells (SCs), however, it remains elusive about its in vivo DNA binding site and roles during cochlear development. Here, by using fresh cochlear tissues and Prox1 antibody, we firstly mapped out the genome-wide binding sites of Prox1 via Cleavage Under Targets and Release Using Nuclease (CUT&RUN). Gene function enrichment analysis suggests several potential functions of Prox1, one of which is regulating cell cycle progression. Secondly, to validate our CUT&RUN data, we further performed in vivo prox1 gain-of-function studies through genetic approaches. Onset of ectopic Prox1 at early embryonic otocyst leads to shorter cochlea with density of HCs and SCs distribution, suggesting a precocious cell cycle exit of cochlear sensory progenitor cells. These findings highlight the power of CUT&RUN in mapping DNA binding sites even in tissues (i.e. cochlea) with rare cells, as well as providing the first genetic evidence to support roles of Prox1 in regulating progenitor pools of cochlear progenitors.
2021-08-06 | GSE146191 | GEO