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不对称之美:造血系统中的不对称分裂与自我更新

The beauty of asymmetry: asymmetric divisions and self-renewal in the haematopoietic system.

作者信息

Ho Anthony D, Wagner Wolfgang

机构信息

Department of Medicine V, University of Heidelberg, Heidelberg, Germany.

出版信息

Curr Opin Hematol. 2007 Jul;14(4):330-6. doi: 10.1097/MOH.0b013e3281900f12.

Abstract

PURPOSE OF REVIEW

The hallmark of stem cells is their dual abilities to self-renew and to differentiate into multiple lineages. To fulfill these functions they must undergo asymmetric division. A central question in developmental biology is how can a single cell divide to produce two progeny cells that adopt different fates? We provided evidence of the significance of asymmetric division in human haematopoietic stem cells.

RECENT FINDINGS

By monitoring the symmetry of divisions of haematopoietic stem cells and following their subsequent developmental potentials at the single cell level, we established a relationship between divisional kinetics and self-renewal capacity. Direct cell-cell contact with cellular determinants in the niche has been shown to play an essential role in maintaining stemness. The creation of in-vitro models for the niche, such as human mesenchymal stromal cells, has provided a controlled laboratory environment in which the relative significance of chemokines and adhesion molecules can be studied.

SUMMARY

Identification of the molecular interactions between stem cells and their niche has led to an understanding of the mechanisms that control the self-renewal of stem cells. Ultimately, molecular signals triggered by adhesion and junction complexes are responsible for the adoption of specific cell fate.

摘要

综述目的

干细胞的标志是其自我更新和分化为多种谱系的双重能力。为了实现这些功能,它们必须进行不对称分裂。发育生物学中的一个核心问题是,一个单细胞如何分裂产生两个具有不同命运的子代细胞?我们提供了不对称分裂在人类造血干细胞中的重要性的证据。

最新发现

通过在单细胞水平监测造血干细胞分裂的对称性并追踪其随后的发育潜能,我们建立了分裂动力学与自我更新能力之间的关系。已证明与龛中的细胞决定因素直接的细胞间接触在维持干性方面起着至关重要的作用。为龛创建体外模型,如人间充质基质细胞,提供了一个可控的实验室环境,在其中可以研究趋化因子和粘附分子的相对重要性。

总结

干细胞与其龛之间分子相互作用的鉴定导致了对控制干细胞自我更新机制的理解。最终,由粘附和连接复合体触发的分子信号负责特定细胞命运的形成。

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