Interleukin-6 Regulates Adult Neural Stem Cell Numbers during Normal and Abnormal Post-natal Development

Autor: Michael P. Fatt, Mekayla Storer, David L. Kaplan, Freda D. Miller, Jaclin V. Simonetta, Denis Gallagher
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Time Factors
medicine.medical_treatment
Neurogenesis
Cell Count
Biochemistry
Article
03 medical and health sciences
neural stem cell
postnatal brain development
Neural Stem Cells
Genetics
medicine
CNS cytokines
Animals
RNA
Messenger
Interleukin 6
Receptor
Pathological
lcsh:QH301-705.5
reproductive and urinary physiology
Cell Proliferation
lcsh:R5-920
biology
Interleukin-6
neural stem cell niche
Cell Biology
stem cell depletion
Receptors
Interleukin-6
Neural stem cell
Olfactory bulb
Cell biology
circulating stem cell factors
adult neurogenesis
Mice
Inbred C57BL
Adult Stem Cells
030104 developmental biology
Cytokine
Animals
Newborn
nervous system
lcsh:Biology (General)
olfactory bulb
Forebrain
biology.protein
Growth and Development
lcsh:Medicine (General)
Developmental Biology
Zdroj: Stem Cell Reports, Vol 10, Iss 5, Pp 1464-1480 (2018)
Stem Cell Reports
ISSN: 2213-6711
Popis: Summary Circulating systemic factors can regulate adult neural stem cell (NSC) biology, but the identity of these circulating cues is still being defined. Here, we have focused on the cytokine interleukin-6 (IL-6), since increased circulating levels of IL-6 are associated with neural pathologies such as autism and bipolar disorder. We show that IL-6 promotes proliferation of post-natal murine forebrain NSCs and that, when the IL-6 receptor is inducibly knocked out in post-natal or adult neural precursors, this causes a long-term decrease in forebrain NSCs. Moreover, a transient circulating surge of IL-6 in perinatal or adult mice causes an acute increase in neural precursor proliferation followed by long-term depletion of adult NSC pools. Thus, IL-6 signaling is both necessary and sufficient for adult NSC self-renewal, and acute perturbations in circulating IL-6, as observed in many pathological situations, have long-lasting effects on the size of adult NSC pools.
Graphical Abstract
Highlights • The cytokine IL-6 promotes self-renewal of post-natal forebrain NSCs • Inducible knockout of the IL-6 receptor causes long-term decreases in post-natal NSCs • A transient surge of circulating IL-6 ultimately depletes adult NSC pools • IL-6 signaling is both necessary and sufficient for adult NSC self-renewal
In this report, Storer and colleagues demonstrate that the circulating cytokine IL-6, which is elevated in humans in different pathological situations, can perturb neural stem cell biology after birth. They show that IL-6 signaling is essential for self-renewal and maintenance of post-natal and adult NSCs in the murine forebrain under normal homeostatic conditions.
Databáze: OpenAIRE
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