Essential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner

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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9b2889ffac5248b398987d01765c8ab0
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spelling	oai:doaj.org-article:9b2889ffac5248b398987d01765c8ab02021-12-02T13:56:55ZEssential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner10.1038/s41598-021-81076-z2045-2322https://doaj.org/article/9b2889ffac5248b398987d01765c8ab02021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81076-zhttps://doaj.org/toc/2045-2322Abstract 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.Naho NomuraChiaki ItoTakako OoshioYuko TadokoroSusumu KohnoMasaya UenoMasahiko KobayashiAtsuko KasaharaYusuke TakaseKenta KurayoshiSha SiChiaki TakahashiMasaaki KomatsuToru YanagawaAtsushi HiraoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Essential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner
description	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.
format	article
author	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
author_facet	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
author_sort	Naho Nomura
title	Essential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner
title_short	Essential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner
title_full	Essential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner
title_fullStr	Essential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner
title_full_unstemmed	Essential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner
title_sort	essential role of autophagy in protecting neonatal haematopoietic stem cells from oxidative stress in a p62-independent manner
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9b2889ffac5248b398987d01765c8ab0
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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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