| First Author | Nomura N | Year | 2021 |
| Journal | Sci Rep | Volume | 11 |
| Issue | 1 | Pages | 1666 |
| PubMed ID | 33462315 | Mgi Jnum | J:300381 |
| Mgi Id | MGI:6502210 | Doi | 10.1038/s41598-021-81076-z |
| Citation | Nomura N, et al. (2021) Essential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner. Sci Rep 11(1):1666 |
| abstractText | 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. |
