title: Boundary cap cells are peripheral nervous system stem cells that can be redirected into central nervous system lineages.
abstract: Boundary cap cells (BC), which express the transcription factor Krox20, participate in the formation of the boundary between the central nervous system and the peripheral nervous system. To study BC stemness, we developed a method to purify and amplify BC in vitro from Krox20(Cre/+), R26R(YFP/+) mouse embryos. We show that BC progeny are EGF/FGF2-responsive, form spheres, and express neural crest markers. Upon growth factor withdrawal, BC progeny gave rise to multiple neural crest and CNS lineages. Transplanted into the developing murine forebrain, they successfully survived, migrated, and integrated within the host environment. Surprisingly, BC progeny generated exclusively CNS cells, including neurons, astrocytes, and myelin-forming oligodendrocytes. In vitro experiments indicated that a sequential combination of ventralizing morphogens and glial growth factors was necessary to reprogram BC into oligodendrocytes. Thus, BC progeny are endowed with differentiation plasticity beyond the peripheral nervous system. The demonstration that CNS developmental cues can reprogram neural crest-derived stem cells into CNS derivatives suggests that BC could serve as a source of cell type-specific lineages, including oligodendrocytes, for cell-based therapies to treat CNS disorders.
authors.affiliation: Centre de Recherche de l'Institut du Cerveau et de Moelle Epinière, Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche S975, 75013 Paris, France.
authors.forename: Violetta
authors.initials: V
authors.lastname: Zujovic
authors.forename: Julie
authors.initials: J
authors.lastname: Thibaud
authors.forename: Corinne
authors.initials: C
authors.lastname: Bachelin
authors.forename: Marie
authors.initials: M
authors.lastname: Vidal
authors.forename: Cyrille
authors.initials: C
authors.lastname: Deboux
authors.forename: Fanny
authors.initials: F
authors.lastname: Coulpier
authors.forename: Nicolas
authors.initials: N
authors.lastname: Stadler
authors.forename: Patrick
authors.initials: P
authors.lastname: Charnay
authors.forename: Piotr
authors.initials: P
authors.lastname: Topilko
authors.forename: Anne
authors.initials: A
authors.lastname: Baron-Van Evercooren
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D002478:Cells, Cultured; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009836:Oligodendroglia / Q000378:metabolism; D017933:Peripheral Nervous System / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*