title: Cell lineage analysis of the mammalian female germline.
abstract: Fundamental aspects of embryonic and post-natal development, including maintenance of the mammalian female germline, are largely unknown. Here we employ a retrospective, phylogenetic-based method for reconstructing cell lineage trees utilizing somatic mutations accumulated in microsatellites, to study female germline dynamics in mice. Reconstructed cell lineage trees can be used to estimate lineage relationships between different cell types, as well as cell depth (number of cell divisions since the zygote). We show that, in the reconstructed mouse cell lineage trees, oocytes form clusters that are separate from hematopoietic and mesenchymal stem cells, both in young and old mice, indicating that these populations belong to distinct lineages. Furthermore, while cumulus cells sampled from different ovarian follicles are distinctly clustered on the reconstructed trees, oocytes from the left and right ovaries are not, suggesting a mixing of their progenitor pools. We also observed an increase in oocyte depth with mouse age, which can be explained either by depth-guided selection of oocytes for ovulation or by post-natal renewal. Overall, our study sheds light on substantial novel aspects of female germline preservation and development.
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yitzhak
authors.initials: Y
authors.lastname: Reizel
authors.forename: Shalev
authors.initials: S
authors.lastname: Itzkovitz
authors.forename: Rivka
authors.initials: R
authors.lastname: Adar
authors.forename: Judith
authors.initials: J
authors.lastname: Elbaz
authors.forename: Adrian
authors.initials: A
authors.lastname: Jinich
authors.forename: Noa
authors.initials: N
authors.lastname: Chapal-Ilani
authors.forename: Yosef E
authors.initials: YE
authors.lastname: Maruvka
authors.forename: Nava
authors.initials: N
authors.lastname: Nevo
authors.forename: Zipora
authors.initials: Z
authors.lastname: Marx
authors.forename: Inna
authors.initials: I
authors.lastname: Horovitz
authors.forename: Adam
authors.initials: A
authors.lastname: Wasserstrom
authors.forename: Avi
authors.initials: A
authors.lastname: Mayo
authors.forename: Irena
authors.initials: I
authors.lastname: Shur
authors.forename: Dafna
authors.initials: D
authors.lastname: Benayahu
authors.forename: Karl
authors.initials: K
authors.lastname: Skorecki
authors.forename: Eran
authors.initials: E
authors.lastname: Segal
authors.forename: Nava
authors.initials: N
authors.lastname: Dekel
authors.forename: Ehud
authors.initials: E
authors.lastname: Shapiro
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D019070:Cell Lineage / Q000235:genetics*; D005260:Female; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D018095:Germ-Line Mutation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D009866:Oogenesis / Q000235:genetics; D009928:Organ Specificity; D010053:Ovary / Q000166:cytology / Q000502:physiology; D010060:Ovulation