Reconstruction of Cell Lineage Trees in Mice

Adam Wasserstrom, Rivka Adar, Gabi Shefer, Dan Frumkin, Shalev Itzkovitz, Tomer Stern, Irena Shur, Lior Zangi, Shai Kaplan, Alon Harmelin, Yair Reisner, Dafna Benayahu (+4 others)
2008 PLoS ONE  
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
more » ... ntal 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.
doi:10.1371/journal.pone.0001939 pmid:18398465 pmcid:PMC2276688 fatcat:dzbmlqbt4zb4nezfu5ahsxzpaa