Niche ‐dependent inhibition of neural stem cell proliferation and oligodendrogenesis is mediated by the presence of myelin basic protein

Myelin basic protein (MBP) presented in the spinal cord niche, but not the brain niche, causes the release of an inhibitory factor that regulates neural precursor cell kinetics and oligodendrogenesis. Hence, regionally distinct niches along the neuraxis respond differently to the same protein (MBP) and regulate cell behavior. AbstractNeural stem and progenitor cells (collectively termed neural precursor cells [NPCs]) are found along the ventricular neuraxis extending from the spinal cord to the forebrain in regionally distinct niches comprised of different cell types, architecture, and cell ‐cell interactions. An understanding of the factors that regulate NPC behavior is critical for developing therapeutics to repair the injured central nervous system. Herein, we demonstrate that myelin basic protein (MBP), the major cytoplasmic protein constituent of the myelin sheath in oligodendro cytes, can regulate NPC behavior. Under physiological conditions, NPCs are not in contact with intracellular MBP; however, upon injury, MBP is released into the neural parenchyma. We reveal that MBP presented in a spinal cord niche is inhibitory to NPC proliferation. This inhibitory effect is region ally distinct as spinal cord NPCs, but not forebrain‐derived NPCs, are inhibited by MBP. We performed coculture and conditioned media experiments that reveal the stem cell niche is a key regulator of MBP's inhibitory actions on NPCs. The inhibition is mediated by a heat‐labile protein released b...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Tissue ‐Specific Stem Cells Source Type: research