Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation
Hearing loss caused by the death of cochlear hair cells (HCs) might be restored through regeneration from supporting cells (SCs) via dedifferentiation and proliferation, as observed in birds. In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SO...
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| Format: | Article |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2022.1096872/full |
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| author | Dorota Piekna-Przybylska Daxiang Na Jingyuan Zhang Cameron Baker John M. Ashton Patricia M. White |
| author_facet | Dorota Piekna-Przybylska Daxiang Na Jingyuan Zhang Cameron Baker John M. Ashton Patricia M. White |
| author_sort | Dorota Piekna-Przybylska |
| collection | DOAJ |
| description | Hearing loss caused by the death of cochlear hair cells (HCs) might be restored through regeneration from supporting cells (SCs) via dedifferentiation and proliferation, as observed in birds. In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. Here we analyze single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2, with the goal of identifying potential secreted effectors. ERBB2 induction in vivo generated a new population of cells with de novo expression of a gene network. Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. We validated mRNA expression of network members, and then extended our analysis to older stages. ERBB2 signaling in young adult SCs also promoted protein expression of gene network members. Furthermore, we found proliferating cochlear cell aggregates in the organ of Corti. Our results suggest that ectopic activation of ERBB2 signaling in cochlear SCs can alter the microenvironment, promoting proliferation and cell rearrangements. Together these results suggest a novel mechanism for inducing stem cell-like activity in the adult mammalian cochlea. |
| first_indexed | 2024-04-11T00:36:08Z |
| format | Article |
| id | doaj.art-9cf99676ae704d6bab349f1edb9ddc3b |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-11T00:36:08Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-9cf99676ae704d6bab349f1edb9ddc3b2023-01-06T19:00:43ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-01-011610.3389/fncel.2022.10968721096872Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activationDorota Piekna-Przybylska0Daxiang Na1Jingyuan Zhang2Cameron Baker3John M. Ashton4Patricia M. White5Department of Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, NY, United StatesDepartment of Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, NY, United StatesDepartment of Biology, University of Rochester, Rochester, NY, United StatesGenomic Research Center, University of Rochester School of Medicine and Dentistry, Rochester, NY, United StatesGenomic Research Center, University of Rochester School of Medicine and Dentistry, Rochester, NY, United StatesDepartment of Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, NY, United StatesHearing loss caused by the death of cochlear hair cells (HCs) might be restored through regeneration from supporting cells (SCs) via dedifferentiation and proliferation, as observed in birds. In a previous report, ERBB2 activation in a subset of cochlear SCs promoted widespread down-regulation of SOX2 in neighboring cells, proliferation, and the differentiation of HC-like cells. Here we analyze single cell transcriptomes from neonatal mouse cochlear SCs with activated ERBB2, with the goal of identifying potential secreted effectors. ERBB2 induction in vivo generated a new population of cells with de novo expression of a gene network. Called small integrin-binding ligand n-linked glycoproteins (SIBLINGs), these ligands and their regulators can alter NOTCH signaling and promote cell survival, proliferation, and differentiation in other systems. We validated mRNA expression of network members, and then extended our analysis to older stages. ERBB2 signaling in young adult SCs also promoted protein expression of gene network members. Furthermore, we found proliferating cochlear cell aggregates in the organ of Corti. Our results suggest that ectopic activation of ERBB2 signaling in cochlear SCs can alter the microenvironment, promoting proliferation and cell rearrangements. Together these results suggest a novel mechanism for inducing stem cell-like activity in the adult mammalian cochlea.https://www.frontiersin.org/articles/10.3389/fncel.2022.1096872/fullcochlear regenerationcandidate pathwayERBB2single cell sequencingSIBLINGCD44 |
| spellingShingle | Dorota Piekna-Przybylska Daxiang Na Jingyuan Zhang Cameron Baker John M. Ashton Patricia M. White Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation Frontiers in Cellular Neuroscience cochlear regeneration candidate pathway ERBB2 single cell sequencing SIBLING CD44 |
| title | Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation |
| title_full | Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation |
| title_fullStr | Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation |
| title_full_unstemmed | Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation |
| title_short | Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation |
| title_sort | single cell rna sequencing analysis of mouse cochlear supporting cell transcriptomes with activated erbb2 receptor indicates a cell specific response that promotes cd44 activation |
| topic | cochlear regeneration candidate pathway ERBB2 single cell sequencing SIBLING CD44 |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2022.1096872/full |
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