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小鼠细胞谱系树的重建。

Reconstruction of cell lineage trees in mice.

作者信息

Wasserstrom Adam, Adar Rivka, Shefer Gabi, Frumkin Dan, Itzkovitz Shalev, Stern Tomer, Shur Irena, Zangi Lior, Kaplan Shai, Harmelin Alon, Reisner Yair, Benayahu Dafna, Tzahor Eldad, Segal Eran, Shapiro Ehud

机构信息

Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.

出版信息

PLoS One. 2008 Apr 9;3(4):e1939. doi: 10.1371/journal.pone.0001939.

Abstract

The cell lineage tree of a multicellular organism represents its history of cell divisions from the very first cell, the zygote. A new method for high-resolution reconstruction of parts of such cell lineage trees was recently developed based on phylogenetic analysis of somatic mutations accumulated during normal development of an organism. In this study we apply this method in mice to reconstruct the lineage trees of distinct cell types. We address for the first time basic questions in developmental biology of higher organisms, namely what is the correlation between the lineage relation among cells and their (1) function, (2) physical proximity and (3) anatomical proximity. We analyzed B-cells, kidney-, mesenchymal- and hematopoietic-stem cells, as well as satellite cells, which are adult skeletal muscle stem cells isolated from their niche on the muscle fibers (myofibers) from various skeletal muscles. Our results demonstrate that all analyzed cell types are intermingled in the lineage tree, indicating that none of these cell types are single exclusive clones. We also show a significant correlation between the physical proximity of satellite cells within muscles and their lineage. Furthermore, we show that satellite cells obtained from a single myofiber are significantly clustered in the lineage tree, reflecting their common developmental origin. Lineage analysis based on somatic mutations enables performing high resolution reconstruction of lineage trees in mice and humans, which can provide fundamental insights to many aspects of their development and tissue maintenance.

摘要

多细胞生物的细胞谱系树代表了其从第一个细胞即受精卵开始的细胞分裂历史。最近基于对生物体正常发育过程中积累的体细胞突变进行系统发育分析,开发了一种用于高分辨率重建此类细胞谱系树部分的新方法。在本研究中,我们将此方法应用于小鼠,以重建不同细胞类型的谱系树。我们首次解决了高等生物发育生物学中的基本问题,即细胞间的谱系关系与其(1)功能、(2)物理距离和(3)解剖学距离之间的相关性。我们分析了B细胞、肾干细胞、间充质干细胞和造血干细胞,以及卫星细胞,卫星细胞是从各种骨骼肌的肌纤维(肌原纤维)上的生态位中分离出来的成年骨骼肌干细胞。我们的结果表明,所有分析的细胞类型在谱系树中相互交织,这表明这些细胞类型中没有一种是单一的排他性克隆。我们还表明,肌肉内卫星细胞的物理距离与其谱系之间存在显著相关性。此外,我们表明从单个肌原纤维获得的卫星细胞在谱系树中显著聚集,反映了它们共同的发育起源。基于体细胞突变的谱系分析能够在小鼠和人类中进行谱系树的高分辨率重建,这可以为它们发育和组织维持的许多方面提供基本见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dd6/2276688/6832235085a5/pone.0001939.g001.jpg

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