論文 - 詳細
| RRC ID | 43866 |
|---|---|
| 著者 | Turinetto V, Orlando L, Sanchez-Ripoll Y, Kumpfmueller B, Storm MP, Porcedda P, Minieri V, Saviozzi S, Accomasso L, Cibrario Rocchietti E, Moorwood K, Circosta P, Cignetti A, Welham MJ, Giachino C. |
| タイトル | High basal γH2AX levels sustain self-renewal of mouse embryonic and induced pluripotent stem cells. |
| ジャーナル | Stem Cells |
| Abstract |
Phosphorylation of histone H2AX (γH2AX) is known to be the earliest indicator of DNA double-strand breaks. Recently, it has been shown that mouse embryonic stem cells (mESCs) have very high basal levels of γH2AX, even when they have not been exposed to genotoxic agents. As the specialized role of high basal γH2AX levels in pluripotent stem cells is still debated, we investigated whether H2AX phosphorylation is important in maintaining self-renewal of these cells. Here, we report that not only mESCs but also mouse-induced pluripotent stem cells (miPSCs), have high basal levels of γH2AX. We show that basal γH2AX levels decrease upon ESC and iPSC differentiation and increase when the cells are treated with self-renewal-enhancing small molecules. We observe that self-renewal activity is highly compromised in H2AX-/- cells and that it can be restored in these cells through reconstitution with a wild-type, but not a phospho-mutated, H2AX construct. Taken together, our findings suggest a novel function of H2AX that expands the knowledge of this histone variant beyond its role in DNA damage and into a new specialized biological function in mouse pluripotent stem cells. |
| 巻・号 | 30(7) |
| ページ | 1414-23 |
| 公開日 | 2012-7-1 |
| DOI | 10.1002/stem.1133 |
| PMID | 22628289 |
| MeSH | Animals DNA Damage / genetics Embryonic Stem Cells / cytology* Embryonic Stem Cells / metabolism* Flow Cytometry Histones / genetics Histones / metabolism* Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / metabolism* Mice Microscopy, Confocal Phosphorylation |
| IF | 6.022 |
| 引用数 | 47 |
| WOS 分野 | BIOTECHNOLOGY & APPLIED MICROBIOLOGY ONCOLOGY HEMATOLOGY CELL & TISSUE ENGINEERING 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 5 |
| 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 | |
| ヒト・動物細胞 | Nanog-iPSC line |