title: Transient maternal IL-6 mediates long-lasting changes in neural stem cell pools by deregulating an endogenous self-renewal pathway.
abstract: The mechanisms that regulate the establishment of adult stem cell pools during normal and perturbed mammalian development are still largely unknown. Here, we asked whether a maternal cytokine surge, which occurs during human maternal infections and has been implicated in cognitive disorders, might have long-lasting consequences for neural stem cell pools in adult progeny. We show that transient, maternally administered interleukin-6 (IL-6) resulted in an expanded adult forebrain neural precursor pool and perturbed olfactory neurogenesis in offspring months after fetal exposure. This increase is likely the long-term consequence of acute hyperactivation of an endogenous autocrine/paracrine IL-6-dependent self-renewal pathway that normally regulates the number of forebrain neural precursors. These studies therefore identify an IL-6-dependent neural stem cell self-renewal pathway in vivo, and support a model in which transiently increased maternal cytokines can act through this pathway in offspring to deregulate neural precursor biology from embryogenesis throughout life.
authors.affiliation: Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, M5G 1L7, Canada; Program in Cell Biology, The Hospital for Sick Children, Toronto, ON, M5G 1L7, Canada; McEwen Center for Regenerative Medicine, University Health Network, Toronto, ON, M5G 1L7, Canada.
authors.forename: Denis
authors.initials: D
authors.lastname: Gallagher
authors.forename: Andreea A
authors.initials: AA
authors.lastname: Norman
authors.forename: Cameron L
authors.initials: CL
authors.lastname: Woodard
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Andrée
authors.initials: A
authors.lastname: Gauthier-Fisher
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujitani
authors.forename: John P
authors.initials: JP
authors.lastname: Vessey
authors.forename: Gonzalo I
authors.initials: GI
authors.lastname: Cancino
authors.forename: Nadia
authors.initials: N
authors.lastname: Sachewsky
authors.forename: Knut
authors.initials: K
authors.lastname: Woltjen
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fatt
authors.forename: Cindi M
authors.initials: CM
authors.lastname: Morshead
authors.forename: David R
authors.initials: DR
authors.lastname: Kaplan
authors.forename: Freda D
authors.initials: FD
authors.lastname: Miller
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D015850:Interleukin-6