論文 - 詳細
| RRC ID | 36679 |
|---|---|
| 著者 | Reinhardt R, Centanin L, Tavhelidse T, Inoue D, Wittbrodt B, Concordet JP, Martinez-Morales JR, Wittbrodt J. |
| タイトル | Sox2, Tlx, Gli3, and Her9 converge on Rx2 to define retinal stem cells in vivo. |
| ジャーナル | EMBO J |
| Abstract |
Transcriptional networks defining stemness in adult neural stem cells (NSCs) are largely unknown. We used the proximal cis-regulatory element (pCRE) of the retina-specific homeobox gene 2 (rx2) to address such a network. Lineage analysis in the fish retina identified rx2 as marker for multipotent NSCs. rx2-positive cells located in the peripheral ciliary marginal zone behave as stem cells for the neuroretina, or the retinal pigmented epithelium. We identified upstream regulators of rx2 interrogating the rx2 pCRE in a trans-regulation screen and focused on four TFs (Sox2, Tlx, Gli3, and Her9) activating or repressing rx2 expression. We demonstrated direct interaction of the rx2 pCRE with the four factors in vitro and in vivo. By conditional mosaic gain- and loss-of-function analyses, we validated the activity of those factors on regulating rx2 transcription and consequently modulating neuroretinal and RPE stem cell features. This becomes obvious by the rx2-mutant phenotypes that together with the data presented above identify rx2 as a transcriptional hub balancing stemness of neuroretinal and RPE stem cells in the adult fish retina. |
| 巻・号 | 34(11) |
| ページ | 1572-88 |
| 公開日 | 2015-6-3 |
| DOI | 10.15252/embj.201490706 |
| PII | embj.201490706 |
| PMID | 25908840 |
| PMC | PMC4474531 |
| MeSH | Adult Stem Cells / cytology Adult Stem Cells / metabolism* Animals Fish Proteins / genetics Fish Proteins / metabolism* Gene Expression Regulation / physiology Homeodomain Proteins / genetics Homeodomain Proteins / metabolism* Neural Stem Cells / cytology Neural Stem Cells / metabolism* Oryzias / genetics Oryzias / metabolism* Retina / cytology Retina / metabolism* Transcription Factors / genetics Transcription Factors / metabolism* |
| IF | 9.889 |
| 引用数 | 26 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| メダカ | GaudiRSG (TG1055) GaudiBBW2.1 (TG1056) |