Loss of Atg2b and Gskip Impairs the Maintenance of the Hematopoietic Stem Cell Pool Size
Open Access
- 8 November 2021
- journal article
- research article
- Published by Taylor & Francis Ltd in Molecular and Cellular Biology
- Vol. 42 (1), e0002421
- https://doi.org/10.1128/mcb.00024-21
Abstract
A germline copy number duplication of chromosome 14q32, which contains ATG2B and GSKIP, was identified in families with myeloproliferative neoplasm (MPN). Herein, we show that mice lacking both Atg2b and Gskip, but not either alone, exhibited decreased hematopoiesis, resulting in death in utero accompanied by anemia. In marked contrast to MPN patients with duplication of ATG2B and GSKIP, the number of hematopoietic stem cells (HSCs), in particular long-term HSCs, in double knockout fetal livers were significantly decreased due to increased cell death. Although the remaining HSCs still had the ability to differentiate into hematopoietic progenitor cells, the differentiation efficiency was quite low. Remarkably, mice with knockout of Atg2b or Gskip alone did not show any hematopoietic abnormality. Mechanistically, while loss of both genes had no effect on autophagy, it increased the expression of genes encoding enzymes involved in oxidative phosphorylation. Taken together, our results indicate that Atg2b and Gskip play a synergistic effect in maintaining the pool size of HSCs.Keywords
Funding Information
- Ministry of Education, Culture, Sports, Science and Technology (19H05706)
- Takeda Science Foundation
- MEXT | Japan Society for the Promotion of Science (A3 foresight program)
- Ministry of Education, Culture, Sports, Science and Technology (19H05706)
This publication has 61 references indexed in Scilit:
- Maintenance of hematopoietic stem cells through regulation of Wnt and mTOR pathwaysNature Medicine, 2012
- STAR: ultrafast universal RNA-seq alignerBioinformatics, 2012
- HIF1α is required for survival maintenance of chronic myeloid leukemia stem cellsBlood, 2012
- Mammalian Atg2 proteins are essential for autophagosome formation and important for regulation of size and distribution of lipid dropletsMolecular Biology of the Cell, 2012
- RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genomeBMC Bioinformatics, 2011
- The autophagy protein Atg7 is essential for hematopoietic stem cell maintenanceThe Journal of Experimental Medicine, 2011
- FIP200 is required for the cell-autonomous maintenance of fetal hematopoietic stem cellsBlood, 2010
- Glycogen Synthase Kinase 3β Interaction Protein Functions as an A-kinase Anchoring ProteinOnline Journal of Public Health Informatics, 2010
- Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxiaProceedings of the National Academy of Sciences of the United States of America, 2007
- Hematopoietic stem cells proliferate until after birth and show a reversible phase-specific engraftment defectJCI Insight, 2006