Single Cell Phenotyping Reveals Heterogeneity Among Hematopoietic Stem Cells Following Infection.

Single Cell Phenotyping Reveals Heterogeneity Among Hematopoietic Stem Cells Following Infection.
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单细胞表型分析揭示了感染后造血干细胞的异质性。

DOI:
10.1002/stem.2692
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发表时间:
2017
期刊:
Stem cells (Dayton, Ohio)
影响因子:
--
通讯作者:
MacLean AL
MacLean AL
中科院分区:
--
文献类型:
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作者:
MacLean AL

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摘要造血干细胞(HSC)的生态位为骨髓内HSC的产生和维持提供了必要的微环境线索。在炎症过程中,造血动力学会受到干扰,但尚不清楚HSC-NICE相互作用是否会因此发生变化。我们直接在体内可视化HSCs,从而能够详细分析旋毛虫感染后小鼠骨髓中的3D生态位动态和迁移模式。对这些HSC轨迹的空间统计分析揭示了HSC行为的两种截然不同的模式:(A)重新访问以前探索的空间的模式和(B)探索新空间的模式。来自对照捐献者的造血干细胞主要遵循模式(A),而来自感染小鼠的造血干细胞则同时采用这两种策略。利用对细胞迁移轨迹和生活史理论的详细计算分析,我们表明感染后HSC移动性的增加可能与直觉相反,使小鼠能够更好地应对感染后HSC-生态位微环境的恶化。
AbstractThe hematopoietic stem cell (HSC) niche provides essential microenvironmental cues for the production and maintenance of HSCs within the bone marrow. During inflammation, hematopoietic dynamics are perturbed, but it is not known whether changes to the HSC–niche interaction occur as a result. We visualize HSCs directly in vivo, enabling detailed analysis of the 3D niche dynamics and migration patterns in murine bone marrow followingTrichinella spiralisinfection. Spatial statistical analysis of these HSC trajectories reveals two distinct modes of HSC behavior: (a) a pattern of revisiting previously explored space and (b) a pattern of exploring new space. Whereas HSCs from control donors predominantly follow pattern (a), those from infected mice adopt both strategies. Using detailed computational analyses of cell migration tracks and life-history theory, we show that the increased motility of HSCs following infection can, perhaps counterintuitively, enable mice to cope better in deteriorating HSC–niche microenvironments following infection.