Dr. Daniel Radecki, Post-doctoral Research Associate, Samanta Lab, “Gpnmb is a novel TGFbeta1 target that negatively regulates neural stem cell remyelination”
February 25 @ 12:00 pm - 1:00 pm
Gpnmb is a Novel TGFbeta1 Target that Negatively Regulates Neural Stem Cell Remyelination
Neural stem cells (NSCs) are an important population of multipotent cells that can differentiate into neurons, astrocytes, and oligodendrocytes in the central nervous system (CNS) during development and adult life. Adult NSCs reside in two main areas in the brain; the sub-granular zone (SGZ) in the hippocampus, and the sub-ventricular zone (SVZ) in the forebrain. This work focuses on the SVZ NSCs, which have the ability to respond during degeneration or injury, where they can migrate and differentiate into neurons, astrocytes, or oligodendrocytes in a context dependent manner. Our lab is interested in demyelinating diseases such as multiple sclerosis (MS), and how NSCs can be targeted to enhance recovery in demyelinating diseases. Through an RNAseq analysis of NSCs during experimental demyelination in mice, we identified glycoprotein non-metastatic melanoma b (GPNMB) and the transforming growth factor beta 1 (TGFb1) pathway as significant regulators of NSCs’ ability to contribute to remyelination. We found that demyelination increased TGFb1 which directly stimulated GPNMB expression in NSCs in vitro, resulting in decreased expression of oligodendrocyte genes and reduced cell number in mouse and human NSCs. In vivo analysis of mice lacking GPNMB showed an increase in oligodendrocytes during remyelination in a GPNMB dose dependent manner, highlighting the negative effect of GPNMB on remyelination and recovery in the CNS. These data indicate that GPNMB is an important regulator of TGFb1 signaling in the CNS, and modulating GPNMB could represent a novel therapeutic path for neurodegenerative diseases.