論文 - 詳細
| RRC ID | 88452 |
|---|---|
| 著者 | Nomura N, Ito C, Ooshio T, Tadokoro Y, Kohno S, Ueno M, Kobayashi M, Kasahara A, Takase Y, Kurayoshi K, Si S, Takahashi C, Komatsu M, Yanagawa T, Hirao A. |
| タイトル | Essential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner. |
| ジャーナル | Sci Rep |
| Abstract |
Autophagy is a cellular degradation system contributing to homeostasis of tissue stem cells including haematopoietic stem cells (HSCs). It plays pleiotropic roles in HSC characteristics throughout life, but its stage-specific roles in HSC self-renewal are unclear. To investigate the effects of Atg5 deletion on stage-specific HSC functions, we compared the repopulating capacity of HSCs in Atg5f/f;Vavi-cre mice from postnatal day (P) 0-7 weeks of age. Interestingly, Atg5 deficiency led to no remarkable abnormality in the HSC self-renewal capacity at P0, but significant defects at P7, followed by severe defects. Induction of Atg5 deletion at P5 by tamoxifen administration to Atg5f/f;Rosa26-Cre-ERT2 mice resulted in normal haematopoiesis, including the HSC population, until around 1 year, suggesting that Atg5 in the early neonatal period was critical for haematopoiesis in adults. Mitochondrial oxidative stress was increased by Atg5 loss in neonatal HSC/progenitor cells. Although p62 had accumulated in immature bone marrow cells of Atg5f/f;Vavi-cre mice, p62 deletion did not restore defective HSC functions, indicating that Atg5-dependent haematopoietic regulation in the developmental period was independent of p62. This study proposes a critical role of autophagy in HSC protection against harsh environments in the early neonatal stage, which is essential for healthy long-term haematopoiesis. |
| 巻・号 | 11(1) |
| ページ | 1666 |
| 公開日 | 2021-1-18 |
| DOI | 10.1038/s41598-021-81076-z |
| PII | 10.1038/s41598-021-81076-z |
| PMID | 33462315 |
| PMC | PMC7814027 |
| MeSH | Animals Animals, Newborn Autophagy / physiology Autophagy-Related Protein 5 / genetics Autophagy-Related Protein 5 / metabolism* Disease Models, Animal Female Hematopoietic Stem Cells / cytology* Hematopoietic Stem Cells / metabolism* Hematopoietic Stem Cells / pathology Male Mice Mice, Knockout Oxidative Stress / physiology Sequestosome-1 Protein / metabolism* |
| IF | 3.998 |
| 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 | 4 |
| 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 | |
| 実験動物マウス | RBRC00806 |