骨髓干细胞在缺氧环境下的新陈代谢机制

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生物通报道  德克萨斯西南医学中心的研究者发现了人体内一种特异的干细胞造血干细胞以独特代谢特性使其能够在低氧环境下生存和增殖。本研究发表在《Cell Stem Cell》杂志上。
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1 U6 P+ k6 X4 o    造血干细胞，存在在骨髓中可快速增殖。一旦被移植，他们将最终分化为血细胞和其他类型的细胞。在造血干细胞转化为血细胞之前，它具有自我更新能力。. V) ^, `) r& z. |+ S, I  L3 S

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    “造血细胞可将葡萄糖或糖类转化为能量而不是通过氧来释放能量，”德克萨斯西南大学内科学系助理教授，本研究的发起者Hesham Sadek说：“它们利用糖酵解而不是线粒体氧化磷酸化满足能量需要。”
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    Sadek和他的研究小组通过流式细胞技术发现了在造血祖细胞和造血干细胞中存在的一种低线粒体活性、糖酵解依赖的细胞亚群，细胞中大量表达Meis1和Hif-1α, Meis1通过转录激活Hif-1α从而调控造血干细胞的新陈代谢。
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    Sadek博士认为更多地了解干细胞功能以及自我更新能力可促使他们找到体外大量培养细胞的新方法。获得可无限培养和生长的骨髓供体细胞可促进干细胞在多种移植治疗中的应用。
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, ]& y8 H, e% K) e( B0 ?9 e    “目前对于干细胞新陈代谢的研究还非常的少，我们的目的是找到干细胞在缺氧环境下新陈代谢和增殖的机制。”Sadek博士说：“多年来骨髓干细胞除了成功的用于骨髓移植，也曾被应用到成百上千的心脏再生研究。我们发现骨髓干细胞具有重要的特性从而在低氧环境下例如心脏病发作后有更大的可能性存活。这些发现有助于基于它的新陈代谢特性选择并富集骨髓干细胞和祖细胞。”

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The Distinct Metabolic Profile of Hematopoietic Stem Cells Reflects Their Location in a Hypoxic Niche
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8 l( g4 A; `- G3 o2 N4 D. JThis article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier.5 o7 E( Y1 R; w

3 [) k- L0 i# v/ s6 n$ VTugba Simsek1, 5, Fatih Kocabas1, 5, Junke Zheng2, 5, Ralph J. DeBerardinis3, Ahmed I. Mahmoud1, Eric N. Olson4, Jay W. Schneider1, Cheng Cheng Zhang2, ,  and Hesham A. Sadek1, , " c- H0 [* }+ P; S6 Q9 ]

$ G% n, l) W& ^$ S: \1 Department of Internal Medicine, Division of Cardiology, UT Southwestern Medical Center, Dallas, TX 75390, USA/ @2 [/ L$ b8 |; r

' p, ~; u8 A/ b% n1 q4 h/ w2 Departments of Physiology and Developmental Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA
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$ ?' q5 n5 [, P5 Z3 Departments of Pediatrics and Genetics, UT Southwestern Medical Center, Dallas, TX 75390, USA
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4 Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA
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4 P( u: p  L  X5 @Received 24 January 2010;  revised 24 May 2010;  accepted 14 July 2010.  Published: September 2, 2010.  Available online 3 September 2010.
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Referred to by:  Hypoxia Signaling in Hematopoietic Stem Cells: A Double-Edged Sword
1 ^7 X+ Q1 D' @Cell Stem Cell, Volume 7, Issue 3, 3 September 2010, Pages 276-278, $ T  d8 ~# r1 g( O- X- n0 |
Patrick J. Pollard, Kamil R. Kranc
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Summary
8 U7 w8 v  z4 U# p3 \- ]Bone marrow transplantation is the primary therapy for numerous hematopoietic disorders. The efficiency of bone marrow transplantation depends on the function of long-term hematopoietic stem cells (LT-HSCs), which is markedly influenced by their hypoxic niche. Survival in this low-oxygen microenvironment requires significant metabolic adaptation. Here, we show that LT-HSCs utilize glycolysis instead of mitochondrial oxidative phosphorylation to meet their energy demands. We used flow cytometry to identify a unique low mitochondrial activity/glycolysis-dependent subpopulation that houses the majority of hematopoietic progenitors and LT-HSCs. Finally, we demonstrate that Meis1 and Hif-1α are markedly enriched in LT-HSCs and that Meis1 regulates HSC metabolism through transcriptional activation of Hif-1α. These findings reveal an important transcriptional network that regulates HSC metabolism.! F6 e* ^+ H8 U* X0 D' x3 [* `
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