Transient Maternal IL-6 Mediates Long-Lasting Changes in Neural Stem Cell Pools by Deregulating an Endogenous Self-Renewal Pathway
| Autor: | Cameron L. Woodard, Gonzalo I. Cancino, Denis Gallagher, Michael P. Fatt, Freda D. Miller, John P. Vessey, Cindi M. Morshead, Andrée Gauthier-Fisher, Masashi Fujitani, Andreea A. Norman, Guang Yang, Nadia Sachewsky, David R. Kaplan, Knut Woltjen |
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| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Offspring Blotting Western Biology Cell Line Mice 03 medical and health sciences Paracrine signalling 0302 clinical medicine Neural Stem Cells Pregnancy Internal medicine medicine Genetics Animals Humans Autocrine signalling Cells Cultured 030304 developmental biology 0303 health sciences Interleukin-6 Reverse Transcriptase Polymerase Chain Reaction Embryogenesis Neurogenesis Cell Differentiation Cell Biology Immunohistochemistry Neural stem cell 3. Good health Cell biology Endocrinology Forebrain Molecular Medicine Female 030217 neurology & neurosurgery Signal Transduction Adult stem cell |
| Zdroj: | Cell Stem Cell. 13(5):564-576 |
| ISSN: | 1934-5909 |
| DOI: | 10.1016/j.stem.2013.10.002 |
| Popis: | SummaryThe 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. |
| Databáze: | OpenAIRE |
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