Increasing cell culture density during a developmental window prevents fated rod precursors derailment toward hybrid rod-glia cells
Abstract In proliferating multipotent retinal progenitors, transcription factors dynamics set the fate of postmitotic daughter cells, but postmitotic cell fate plasticity driven by extrinsic factors remains controversial. Transcriptome analysis reveals the concurrent expression by postmitotic rod pr...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-32571-y |
| _version_ | 1797845977905758208 |
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| author | Ivana Barravecchia Chiara De Cesari Viviana Guadagni Giovanni Signore Edoardo Bertolini Serena Gea Giannelli Francesca Scebba Davide Martini Mario Enrico Pè Vania Broccoli Massimiliano Andreazzoli Debora Angeloni Gian Carlo Demontis |
| author_facet | Ivana Barravecchia Chiara De Cesari Viviana Guadagni Giovanni Signore Edoardo Bertolini Serena Gea Giannelli Francesca Scebba Davide Martini Mario Enrico Pè Vania Broccoli Massimiliano Andreazzoli Debora Angeloni Gian Carlo Demontis |
| author_sort | Ivana Barravecchia |
| collection | DOAJ |
| description | Abstract In proliferating multipotent retinal progenitors, transcription factors dynamics set the fate of postmitotic daughter cells, but postmitotic cell fate plasticity driven by extrinsic factors remains controversial. Transcriptome analysis reveals the concurrent expression by postmitotic rod precursors of genes critical for the Müller glia cell fate, which are rarely generated from terminally-dividing progenitors as a pair with rod precursors. By combining gene expression and functional characterisation in single cultured rod precursors, we identified a time-restricted window where increasing cell culture density switches off the expression of genes critical for Müller glial cells. Intriguingly, rod precursors in low cell culture density maintain the expression of genes of rod and glial cell fate and develop a mixed rod/Muller glial cells electrophysiological fingerprint, revealing rods derailment toward a hybrid rod-glial phenotype. The notion of cell culture density as an extrinsic factor critical for preventing rod-fated cells diversion toward a hybrid cell state may explain the occurrence of hybrid rod/MG cells in the adult retina and provide a strategy to improve engraftment yield in regenerative approaches to retinal degenerative disease by stabilising the fate of grafted rod precursors. |
| first_indexed | 2024-04-09T17:48:41Z |
| format | Article |
| id | doaj.art-dab0c647c8294922ac3b468facc4ad7e |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T17:48:41Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-dab0c647c8294922ac3b468facc4ad7e2023-04-16T11:13:38ZengNature PortfolioScientific Reports2045-23222023-04-0113111710.1038/s41598-023-32571-yIncreasing cell culture density during a developmental window prevents fated rod precursors derailment toward hybrid rod-glia cellsIvana Barravecchia0Chiara De Cesari1Viviana Guadagni2Giovanni Signore3Edoardo Bertolini4Serena Gea Giannelli5Francesca Scebba6Davide Martini7Mario Enrico Pè8Vania Broccoli9Massimiliano Andreazzoli10Debora Angeloni11Gian Carlo Demontis12Department of Pharmacy, University of PisaScuola Superiore Sant’AnnaDepartment of Biology, University of PisaDepartment of Biology, University of PisaScuola Superiore Sant’AnnaSan Raffaele HospitalScuola Superiore Sant’AnnaDepartment of Biology, University of PisaScuola Superiore Sant’AnnaSan Raffaele HospitalDepartment of Biology, University of PisaScuola Superiore Sant’AnnaDepartment of Pharmacy, University of PisaAbstract In proliferating multipotent retinal progenitors, transcription factors dynamics set the fate of postmitotic daughter cells, but postmitotic cell fate plasticity driven by extrinsic factors remains controversial. Transcriptome analysis reveals the concurrent expression by postmitotic rod precursors of genes critical for the Müller glia cell fate, which are rarely generated from terminally-dividing progenitors as a pair with rod precursors. By combining gene expression and functional characterisation in single cultured rod precursors, we identified a time-restricted window where increasing cell culture density switches off the expression of genes critical for Müller glial cells. Intriguingly, rod precursors in low cell culture density maintain the expression of genes of rod and glial cell fate and develop a mixed rod/Muller glial cells electrophysiological fingerprint, revealing rods derailment toward a hybrid rod-glial phenotype. The notion of cell culture density as an extrinsic factor critical for preventing rod-fated cells diversion toward a hybrid cell state may explain the occurrence of hybrid rod/MG cells in the adult retina and provide a strategy to improve engraftment yield in regenerative approaches to retinal degenerative disease by stabilising the fate of grafted rod precursors.https://doi.org/10.1038/s41598-023-32571-y |
| spellingShingle | Ivana Barravecchia Chiara De Cesari Viviana Guadagni Giovanni Signore Edoardo Bertolini Serena Gea Giannelli Francesca Scebba Davide Martini Mario Enrico Pè Vania Broccoli Massimiliano Andreazzoli Debora Angeloni Gian Carlo Demontis Increasing cell culture density during a developmental window prevents fated rod precursors derailment toward hybrid rod-glia cells Scientific Reports |
| title | Increasing cell culture density during a developmental window prevents fated rod precursors derailment toward hybrid rod-glia cells |
| title_full | Increasing cell culture density during a developmental window prevents fated rod precursors derailment toward hybrid rod-glia cells |
| title_fullStr | Increasing cell culture density during a developmental window prevents fated rod precursors derailment toward hybrid rod-glia cells |
| title_full_unstemmed | Increasing cell culture density during a developmental window prevents fated rod precursors derailment toward hybrid rod-glia cells |
| title_short | Increasing cell culture density during a developmental window prevents fated rod precursors derailment toward hybrid rod-glia cells |
| title_sort | increasing cell culture density during a developmental window prevents fated rod precursors derailment toward hybrid rod glia cells |
| url | https://doi.org/10.1038/s41598-023-32571-y |
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