| Autor: |
Naho Nomura, Chiaki Ito, Takako Ooshio, Yuko Tadokoro, Susumu Kohno, Masaya Ueno, Masahiko Kobayashi, Atsuko Kasahara, Yusuke Takase, Kenta Kurayoshi, Sha Si, Chiaki Takahashi, Masaaki Komatsu, Toru Yanagawa, Atsushi Hirao |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2045-2322 |
| DOI: |
10.1038/s41598-021-81076-z |
| Popis: |
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 Atg5 f/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 Atg5 f/f ;Rosa26-Cre-ER T2 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 Atg5 f/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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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