Autophagy is dispensable for the maintenance of hematopoietic stem cells in neonates

Author:

Hashimoto Michihiro1ORCID,Umemoto Terumasa1ORCID,Nakamura-Ishizu Ayako23ORCID,Matsumura Takayoshi2,Yokomizo Tomomasa1,Sezaki Maiko1,Takizawa Hitoshi1ORCID,Suda Toshio12ORCID

Affiliation:

1. International Research Center for Medical Sciences, Kumamoto University, Kumamoto City, Japan;

2. Cancer Science Institute, National University of Singapore, Singapore; and

3. Department of Anatomy and Developmental Biology, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan

Abstract

Abstract Hematopoietic stem cells (HSCs) undergo self-renewal or differentiation to sustain lifelong hematopoiesis. HSCs are preserved in quiescence with low mitochondrial activity. Recent studies indicate that autophagy contributes to HSC quiescence through suppressing mitochondrial metabolism. However, it remains unclear whether autophagy is involved in the regulation of neonatal HSCs, which proliferate actively. In this study, we clarified the role of autophagy in neonatal HSCs using 2 types of autophagy-related gene 7 (Atg7)-conditional knockout mice: Mx1-Cre inducible system and Vav-Cre system. Atg7-deficient HSCs exhibited excess cell divisions with enhanced mitochondrial metabolism, leading to bone marrow failure at adult stage. However, Atg7 deficiency minimally affected hematopoiesis and metabolic state in HSCs at neonatal stage. In addition, Atg7-deficient neonatal HSCs exhibited long-term reconstructing activity, equivalent to wild-type neonatal HSCs. Taken together, autophagy is dispensable for stem cell function and hematopoietic homeostasis in neonates and provide a novel aspect into the role of autophagy in the HSC regulation.

Publisher

American Society of Hematology

Subject

Hematology

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