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论文题目: The mitochondrial respiratory chain is essential for haematopoietic stem cell function
英文论文题目: The mitochondrial respiratory chain is essential for haematopoietic stem cell function
第一作者: Anso, E; Weinberg, SE; Diebold, LP; Thompson, BJ; Malinge, S; Schumacker, PT; Liu, X; Zhang, YY; Shao, Z; Steadman, M; Marsh, KM; Xu, J; Crispino, JD; Chandel, NS
英文第一作者: Anso, E; Weinberg, SE; Diebold, LP; Thompson, BJ; Malinge, S; Schumacker, PT; Liu, X; Zhang, YY; Shao, Z; Steadman, M; Marsh, KM; Xu, J; Crispino, JD; Chandel, NS
联系作者: Chandel, NS (reprint author), Robert H Lurie Canc Ctr, Dept Med, Chicago, IL 60611 USA.
英文联系作者: Chandel, NS (reprint author), Robert H Lurie Canc Ctr, Dept Med, Chicago, IL 60611 USA.
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发表年度: 2017
卷: 19
期: 6
页码: 614-+
摘要: Adult and fetal haematopoietic stem cells (HSCs) display a glycolytic phenotype, which is required for maintenance of stemness; however, whether mitochondrial respiration is required to maintain HSC function is not known. Here we report that loss of the mitochondrial complex III subunit Rieske iron-sulfur protein (RISP) in fetal mouse HSCs allows them to proliferate but impairs their differentiation, resulting in anaemia and prenatal death. RISP-null fetal HSCs displayed impaired respiration resulting in a decreased NAD(+)/NADH ratio. RISP-null fetal HSCs and progenitors exhibited an increase in both DNA and histone methylation associated with increases in 2-hydroxyglutarate (2HG), a metabolite known to inhibit DNA and histone demethylases. RISP inactivation in adult HSCs also impaired respiration resulting in loss of quiescence concomitant with severe pancytopenia and lethality. Thus, respiration is dispensable for adult or fetal HSC proliferation, but essential for fetal HSC differentiation and maintenance of adult HSC quiescence.
英文摘要: Adult and fetal haematopoietic stem cells (HSCs) display a glycolytic phenotype, which is required for maintenance of stemness; however, whether mitochondrial respiration is required to maintain HSC function is not known. Here we report that loss of the mitochondrial complex III subunit Rieske iron-sulfur protein (RISP) in fetal mouse HSCs allows them to proliferate but impairs their differentiation, resulting in anaemia and prenatal death. RISP-null fetal HSCs displayed impaired respiration resulting in a decreased NAD(+)/NADH ratio. RISP-null fetal HSCs and progenitors exhibited an increase in both DNA and histone methylation associated with increases in 2-hydroxyglutarate (2HG), a metabolite known to inhibit DNA and histone demethylases. RISP inactivation in adult HSCs also impaired respiration resulting in loss of quiescence concomitant with severe pancytopenia and lethality. Thus, respiration is dispensable for adult or fetal HSC proliferation, but essential for fetal HSC differentiation and maintenance of adult HSC quiescence.
刊物名称: NATURE CELL BIOLOGY
英文刊物名称: NATURE CELL BIOLOGY
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学科: Cell Biology
英文学科: Cell Biology
影响因子: 20.06
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论文类别: Article
英文论文类别: Article
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