Wnt signalling facilitates neuronal differentiation of cochlear Frizzled10-positive cells in mouse cochlea via glypican 6 modulation
Abstract Degeneration of cochlear spiral ganglion neurons (SGNs) leads to irreversible sensorineural hearing loss (SNHL), as SGNs lack regenerative capacity. Although cochlear glial cells (GCs) have some neuronal differentiation potential, their specific identities remain unclear. This study identif...
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2025-01-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02039-9 |
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| author | Man Wang Yuechen Han Weibin An Xue Wang Fang Chen Junze Lu Yu Meng Yan Li Yanqing Wang Jingxin Li Chunjie Zhao Renjie Chai Haibo Wang Wenwen Liu Lei Xu |
| author_facet | Man Wang Yuechen Han Weibin An Xue Wang Fang Chen Junze Lu Yu Meng Yan Li Yanqing Wang Jingxin Li Chunjie Zhao Renjie Chai Haibo Wang Wenwen Liu Lei Xu |
| author_sort | Man Wang |
| collection | DOAJ |
| description | Abstract Degeneration of cochlear spiral ganglion neurons (SGNs) leads to irreversible sensorineural hearing loss (SNHL), as SGNs lack regenerative capacity. Although cochlear glial cells (GCs) have some neuronal differentiation potential, their specific identities remain unclear. This study identifies a distinct subpopulation, Frizzled10 positive (FZD10+) cells, as an important type of GC responsible for neuronal differentiation in mouse cochlea. FZD10 + cells can differentiate into various SGN subtypes in vivo, adhering to natural proportions. Wnt signaling enhances the ability of FZD10 + cells to function as neural progenitors and increases the neuronal excitability of the FZD10–derived neurons. Single-cell RNA sequencing analysis characterizes FZD10-derived differentiating cell populations, while crosstalk network analysis identifies multiple signaling pathways and target genes influenced by Wnt signaling that contribute to the function of FZD10 + cells as neural progenitors. Pseudotime analysis maps the differentiation trajectory from proliferated GCs to differentiating neurons. Further experiments indicate that glypican 6 (GPC6) may regulate this neuronal lineage, while GPC6 deficiency diminishes the effects of Wnt signaling on FZD10–derived neuronal differentiation and synapse formation. These findings suggest the critical role of Wnt signaling in the neuronal differentiation derived from cochlear FZD10 + cells and provide insights into the mechanisms potentially involved in this process. |
| format | Article |
| id | doaj-art-b73d7438e7d74cb195f6098178c84484 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Cell Communication and Signaling |
| spelling | doaj-art-b73d7438e7d74cb195f6098178c844842025-02-02T12:34:32ZengBMCCell Communication and Signaling1478-811X2025-01-0123112110.1186/s12964-025-02039-9Wnt signalling facilitates neuronal differentiation of cochlear Frizzled10-positive cells in mouse cochlea via glypican 6 modulationMan Wang0Yuechen Han1Weibin An2Xue Wang3Fang Chen4Junze Lu5Yu Meng6Yan Li7Yanqing Wang8Jingxin Li9Chunjie Zhao10Renjie Chai11Haibo Wang12Wenwen Liu13Lei Xu14Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong UniversityDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong UniversityDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong UniversityDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong UniversityDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong UniversityDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong UniversityDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong UniversityTranslational Medical Research Centre, The First Hospital Affiliated to Shandong First Medical University& Shandong Provincial Qianfoshan HospitalDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong UniversityKey Laboratory of Developmental Genes and Human Diseases, School of Medicine, Ministry of Education, Southeast UniversityKey Laboratory of Developmental Genes and Human Diseases, School of Medicine, Ministry of Education, Southeast UniversityDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong UniversityDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong UniversityDepartment of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong UniversityAbstract Degeneration of cochlear spiral ganglion neurons (SGNs) leads to irreversible sensorineural hearing loss (SNHL), as SGNs lack regenerative capacity. Although cochlear glial cells (GCs) have some neuronal differentiation potential, their specific identities remain unclear. This study identifies a distinct subpopulation, Frizzled10 positive (FZD10+) cells, as an important type of GC responsible for neuronal differentiation in mouse cochlea. FZD10 + cells can differentiate into various SGN subtypes in vivo, adhering to natural proportions. Wnt signaling enhances the ability of FZD10 + cells to function as neural progenitors and increases the neuronal excitability of the FZD10–derived neurons. Single-cell RNA sequencing analysis characterizes FZD10-derived differentiating cell populations, while crosstalk network analysis identifies multiple signaling pathways and target genes influenced by Wnt signaling that contribute to the function of FZD10 + cells as neural progenitors. Pseudotime analysis maps the differentiation trajectory from proliferated GCs to differentiating neurons. Further experiments indicate that glypican 6 (GPC6) may regulate this neuronal lineage, while GPC6 deficiency diminishes the effects of Wnt signaling on FZD10–derived neuronal differentiation and synapse formation. These findings suggest the critical role of Wnt signaling in the neuronal differentiation derived from cochlear FZD10 + cells and provide insights into the mechanisms potentially involved in this process.https://doi.org/10.1186/s12964-025-02039-9Wnt signaling pathwayFrizzled10Glial cellsProliferationNeuronal differentiationSpiral ganglion neurons |
| spellingShingle | Man Wang Yuechen Han Weibin An Xue Wang Fang Chen Junze Lu Yu Meng Yan Li Yanqing Wang Jingxin Li Chunjie Zhao Renjie Chai Haibo Wang Wenwen Liu Lei Xu Wnt signalling facilitates neuronal differentiation of cochlear Frizzled10-positive cells in mouse cochlea via glypican 6 modulation Cell Communication and Signaling Wnt signaling pathway Frizzled10 Glial cells Proliferation Neuronal differentiation Spiral ganglion neurons |
| title | Wnt signalling facilitates neuronal differentiation of cochlear Frizzled10-positive cells in mouse cochlea via glypican 6 modulation |
| title_full | Wnt signalling facilitates neuronal differentiation of cochlear Frizzled10-positive cells in mouse cochlea via glypican 6 modulation |
| title_fullStr | Wnt signalling facilitates neuronal differentiation of cochlear Frizzled10-positive cells in mouse cochlea via glypican 6 modulation |
| title_full_unstemmed | Wnt signalling facilitates neuronal differentiation of cochlear Frizzled10-positive cells in mouse cochlea via glypican 6 modulation |
| title_short | Wnt signalling facilitates neuronal differentiation of cochlear Frizzled10-positive cells in mouse cochlea via glypican 6 modulation |
| title_sort | wnt signalling facilitates neuronal differentiation of cochlear frizzled10 positive cells in mouse cochlea via glypican 6 modulation |
| topic | Wnt signaling pathway Frizzled10 Glial cells Proliferation Neuronal differentiation Spiral ganglion neurons |
| url | https://doi.org/10.1186/s12964-025-02039-9 |
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