Essential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner
In: Scientific Reports Scientific Reports, Jg. 11 (2021), Heft 1, S. 1-14
Online
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Zugriff:
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.
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Essential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner
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Autor/in / Beteiligte Person: | Si, Sha ; Kasahara, Atsuko ; Kohno, Susumu ; Kurayoshi, Kenta ; Yanagawa, Toru ; Tadokoro, Yuko ; Nomura, Naho ; Kobayashi, Masahiko ; Ooshio, Takako ; Takahashi, Chiaki ; Takase, Yusuke ; Ueno, Masaya ; Hirao, Atsushi ; Ito, Chiaki ; Komatsu, Masaaki |
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Zeitschrift: | Scientific Reports Scientific Reports, Jg. 11 (2021), Heft 1, S. 1-14 |
Veröffentlichung: | 2020 |
Medientyp: | unknown |
ISSN: | 2045-2322 (print) |
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