ATP turnover and glucose dependency in hematopoietic stem/progenitor cells are increased by proliferation and differentiation
ATP turnover and glucose dependency in hematopoietic stem/progenitor cells are increased by proliferation and differentiation
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DOI：
10.1016/j.bbrc.2019.04.123
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发表时间：
2019-06-18
影响因子：
3.1
通讯作者：
Takubo, Keiyo
中科院分区：
文献类型：
--
作者：
Watanuki, Shintaro;Kobayashi, Hiroshi;Takubo, Keiyo
造血干细胞 (HSC) 是骨髓生态位中的静止细胞，相对依赖于糖酵解 ATP 的产生。另一方面，分化细胞，包括造血祖细胞 (HPC)，优先通过氧化磷酸化产生 ATP。然而，尚不清楚细胞分化和细胞周期状态如何影响 HSC 和 HPC 的营养需求和 ATP 产生。使用新开发的培养系统，我们证明 HPC 的存活强烈依赖于葡萄糖，而静止的 HSC 在没有葡萄糖的情况下也能存活一段时间。在 HPC 中，粒细胞/单核细胞祖细胞 (GMP) 在增殖过程中特别依赖于葡萄糖。通过监测活细胞中的 ATP 浓度，我们证明在 HSC 中没有葡萄糖的情况下，ATP 水平可以在短时间内维持，这可能是由于它们的代谢灵活性。此外，HSC 表现出较低的 ATP 周转率，而包括 GMP 在内的 HPC 则表现出较高的 ATP 周转率，并且需要从葡萄糖中高效生产 ATP。这些发现表明，根据细胞周期和分化状态，HSC 和 HPC 之间的 ATP 周转和营养需求有所不同。 (C) 2019 Elsevier Inc. 保留所有权利。
Hematopoietic stem cells (HSCs) are quiescent cells in the bone marrow niche and are relatively dependent on glycolytic ATP production. On the other hand, differentiated cells, including hematopoietic progenitor cells (HPCs), preferentially generate ATP via oxidative phosphorylation. However, it is unclear how cellular differentiation and the cell cycle status affect nutritional requirements and ATP production in HSCs and HPCs. Using a newly developed culture system, we demonstrated that survival of HPCs was strongly dependent on glucose, whereas quiescent HSCs survived for a certain duration without glucose. Among HPCs, granulocyte/monocyte progenitors (GMPs) were particularly dependent on glucose during proliferation. By monitoring the ATP concentration in live cells, we demonstrated that the ATP level was maintained for a short duration without glucose in HSCs, possibly due to their metabolic flexibility. In addition, HSCs exhibited low ATP turnover, whereas HPCs including GMPs demonstrated high ATP turnover and required efficient ATP production from glucose. These findings show that ATP turnover and nutritional requirements differ between HSCs and HPCs according to the cell cycle and differentiation status. (C) 2019 Elsevier Inc. All rights reserved.