Reconstruction of cell lineage trees in mice.
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.
Wasserstrom
Adam
A
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
Adar
Rivka
R
Shefer
Gabi
G
Frumkin
Dan
D
Itzkovitz
Shalev
S
Stern
Tomer
T
Shur
Irena
I
Zangi
Lior
L
Kaplan
Shai
S
Harmelin
Alon
A
Reisner
Yair
Y
Benayahu
Dafna
D
Tzahor
Eldad
E
Segal
Eran
E
Shapiro
Ehud
E
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D006412:Hematopoietic Stem Cells / Q000166:cytology; D007668:Kidney / Q000166:cytology; D007694:Killer Cells, Natural / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology; D013234:Stem Cells / Q000166:cytology*