title: Multipotency of Adult Hippocampal NSCs In Vivo Is Restricted by Drosha/NFIB.
abstract: Adult neural stem cells (NSCs) are defined by their inherent capacity to self-renew and give rise to neurons, astrocytes, and oligodendrocytes. In vivo, however, hippocampal NSCs do not generate oligodendrocytes for reasons that have remained enigmatic. Here, we report that deletion of Drosha in adult dentate gyrus NSCs activates oligodendrogenesis and reduces neurogenesis at the expense of gliogenesis. We further find that Drosha directly targets NFIB to repress its expression independently of Dicer and microRNAs. Knockdown of NFIB in Drosha-deficient hippocampal NSCs restores neurogenesis, suggesting that the Drosha/NFIB mechanism robustly prevents oligodendrocyte fate acquisition in vivo. Taken together, our findings establish that adult hippocampal NSCs inherently possess multilineage potential but that Drosha functions as a molecular barrier preventing oligodendrogenesis.
authors.affiliation: Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland.
authors.forename: Chiara
authors.initials: C
authors.lastname: Rolando
authors.affiliation: Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Erni
authors.affiliation: Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland.
authors.forename: Alice
authors.initials: A
authors.lastname: Grison
authors.affiliation: Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland.
authors.forename: Robert
authors.initials: R
authors.lastname: Beattie
authors.affiliation: Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Engler
authors.affiliation: Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Gokhale
authors.affiliation: Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Milo
authors.affiliation: Brain Research Institute, Faculty of Medicine and Science, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wegleiter
authors.affiliation: Brain Research Institute, Faculty of Medicine and Science, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jessberger
authors.affiliation: Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland. Electronic address: verdon.taylor@unibas.ch.
authors.forename: Verdon
authors.initials: V
authors.lastname: Taylor
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D018891:Dentate Gyrus / Q000166:cytology; D017353:Gene Deletion; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism*
chemical_list: D051839:NFI Transcription Factors; C484683:Nfib protein, mouse; D012333:RNA, Messenger; C513400:Drosha protein, mouse; D043244:Ribonuclease III