Pericytes Favor Oligodendrocyte Fate Choice in Adult Neural Stem Cells

Maria Elena Silva, Simona Lange, Bryan Hinrichsen, Amber R Philp, Carolina R Reyes, Diego Halabi, Josselyne B Mansilla, Peter Rotheneichner, Alerie Guzman de la Fuente, Sebastien Couillard-Despres, Luis F Bátiz, Robin J M Franklin, Ludwig Aigner, Francisco J Rivera

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Upon demyelination, oligodendrocyte progenitor cells (OPCs) are activated and they proliferate, migrate and differentiate into myelin-producing oligodendrocytes. Besides OPCs, neural stem cells (NSCs) may respond to demyelination and generate oligodendrocytes. We have recently shown that CNS-resident pericytes (PCs) respond to demyelination, proliferate and secrete Laminin alpha2 (Lama2) that, in turn, enhances OPC differentiation. Here, we aimed to evaluate whether PCs influence the fate choice of NSCs in vitro, towards the production of new myelin-producing cells. Indeed, upon exposure to conditioned medium derived from PCs (PC-CM), the majority of NSCs gave rise to GalC- and myelin basic protein (MBP)-expressing oligodendrocytes at the expense of the generation of GFAP-positive astrocytes. Consistent with these findings, PC-CM induces an increase in the expression of the oligodendrocyte fate determinant Olig2, while the expression level of the astrocyte determinant ID2 is decreased. Finally, pre-incubation of PC-CM with an anti-Lama2 antibody prevented the generation of oligodendrocytes. Our findings indicate that PCs-derived Lama2 instructs NSCs to an oligodendrocyte fate choice favoring the generation of myelin-producing cells at the expense of astrocytes in vitro. Further studies aiming to reveal the role of PCs during remyelination may pave the way for the development of new therapies for the treatment of MS.

Original languageEnglish
Article number85
Number of pages7
JournalFrontiers in cellular neuroscience
Volume13
DOIs
Publication statusPublished - 27 Mar 2019

Fingerprint Dive into the research topics of 'Pericytes Favor Oligodendrocyte Fate Choice in Adult Neural Stem Cells'. Together they form a unique fingerprint.

  • Cite this

    Silva, M. E., Lange, S., Hinrichsen, B., Philp, A. R., Reyes, C. R., Halabi, D., Mansilla, J. B., Rotheneichner, P., Guzman de la Fuente, A., Couillard-Despres, S., Bátiz, L. F., Franklin, R. J. M., Aigner, L., & Rivera, F. J. (2019). Pericytes Favor Oligodendrocyte Fate Choice in Adult Neural Stem Cells. Frontiers in cellular neuroscience, 13, [85]. https://doi.org/10.3389/fncel.2019.00085