| 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*
|
| リソース情報 |
| 実験動物マウス |
RBRC00806 |
