title: Adhesion is prerequisite, but alone insufficient, to elicit stem cell pluripotency.
abstract: Primitive mammalian neural stem cells (NSCs), arising during the earliest stages of embryogenesis, possess pluripotency in embryo chimera assays in contrast to definitive NSCs found in the adult. We hypothesized that adhesive differences determine the association of stem cells with embryonic cells in chimera assays and hence their ability to contribute to later tissues. We show that primitive NSCs and definitive NSCs possess adhesive differences, resulting from differential cadherin expression, that lead to a double dissociation in outcomes after introduction into the early- versus midgestation embryo. Primitive NSCs are able to sort with the cells of the inner cell mass and thus contribute to early embryogenesis, in contrast to definitive NSCs, which cannot. Conversely, primitive NSCs sort away from cells of the embryonic day 9.5 telencephalon and are unable to contribute to neural tissues at midembryogenesis, in contrast to definitive NSCs, which can. Overcoming these adhesive differences by E-cadherin overexpression allows some definitive NSCs to integrate into the inner cell mass but is insufficient to allow them to contribute to later development. These adhesive differences suggest an evolving compartmentalization in multipotent NSCs during development and serve to illustrate the importance of cell-cell association for revealing cellular contribution.
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 1A8. phillip.karpowicz@utoronto.ca
authors.forename: Phillip
authors.initials: P
authors.lastname: Karpowicz
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Inoue
authors.forename: Sue
authors.initials: S
authors.lastname: Runciman
authors.forename: Brian
authors.initials: B
authors.lastname: Deveale
authors.forename: Raewyn
authors.initials: R
authors.lastname: Seaberg
authors.forename: Marina
authors.initials: M
authors.lastname: Gertsenstein
authors.forename: Lois
authors.initials: L
authors.lastname: Byers
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Yamanaka
authors.forename: Sandra
authors.initials: S
authors.lastname: Tondat
authors.forename: John
authors.initials: J
authors.lastname: Slevin
authors.forename: Seiji
authors.initials: S
authors.lastname: Hitoshi
authors.forename: Janet
authors.initials: J
authors.lastname: Rossant
authors.forename: Derek
authors.initials: D
authors.lastname: van der Kooy
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology*; D011247:Pregnancy