Transient Maternal IL-6 Mediates Long-Lasting Changes in Neural Stem Cell Pools by Deregulating an Endogenous Self-Renewal Pathway

• DOI: 10.1016/j.stem.2013.10.002
• Publication Date: 2013-11-07T16:50:49Z
• Authors: Denis Gallagher; Andreea A. Norman; Cameron L. Woodard; Guang Yang; Andrée Gauthier-F...; Masashi Fujitani; John P. Vessey; Gonzalo I. Cancino; Nadia Sachewsky; Knut Woltjen; Michael P. Fatt; Cindi M. Morshead; David R. Kaplan; Freda D. Miller
• Keywords: 0301 basic medicine; Interleukin-6; Reverse Transcriptase Polymerase Chain Reaction; Blotting, Western; Cell Differentiation; Cell Biology; Immunohistochemistry; Cell Line; Mice; 03 medical and health sciences; Neural Stem Cells; Pregnancy; Genetics; Molecular Medicine; Animals; Humans; Female; Cells, Cultured; Signal Transduction

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.