Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo
Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo
复制标题
DOI：
10.1101/475905
复制
发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Hiroshi Kobayashi;T. Morikawa;Ayumi Okinaga;F. Hamano;T. Hashidate‐Yoshida;Shintaro Watanuki;D. Hishikawa;H. Shindou;F. Arai;Y. Kabe;M. Suematsu;Takao Shimizu;K. Takubo
中科院分区：
文献类型：
--
作者：
Hiroshi Kobayashi;T. Morikawa;Ayumi Okinaga;F. Hamano;T. Hashidate‐Yoshida;Shintaro Watanuki;D. Hishikawa;H. Shindou;F. Arai;Y. Kabe;M. Suematsu;Takao Shimizu;K. Takubo
造血干细胞（HSC）通过在骨髓小生境中保持静止来维持终身造血。由于细胞在体外快速增殖和分化，在培养物中尚未实现静止状态的重演。在详尽分析不同的环境因素组合和浓度作为模拟生理条件的一种方式后，我们能够在非常低的细胞因子浓度、缺氧和非常高的脂肪酸水平下在培养物中维持可移植的静止HSC 1个月。需要外源性脂肪酸可能是由于缺氧和低细胞因子条件抑制内源性脂肪酸合成。相反，高浓度的细胞因子或常氧诱导HSC增殖和分化。我们的新的培养系统提供了一种手段来评估稳态HSC的特性，并在接近生理条件下在体外测试确定的因素的影响。
Hematopoietic stem cells (HSCs) maintain lifelong hematopoiesis by remaining quiescent in the bone marrow niche. Recapitulation of a quiescent state in culture has not been achieved, as cells rapidly proliferate and differentiate in vitro. After exhaustive analysis of different environmental factor combinations and concentrations as a way to mimic physiological conditions, we were able to maintain engraftable quiescent HSCs for 1 month in culture under very low cytokine concentrations, hypoxia, and very high fatty acid levels. Exogenous fatty acids were required likely due to suppression of intrinsic fatty acid synthesis by hypoxia and low cytokine conditions. By contrast, high cytokine concentrations or normoxia induced HSC proliferation and differentiation. Our novel culture system provides a means to evaluate properties of steady state HSCs and test effects of defined factors in vitro under near-physiological conditions.