TY - JOUR
T1 - Adult rat myelin enhances axonal outgrowth from neural stem cells
AU - Poplawski, Gunnar H.D.
AU - Lie, Richard
AU - Hunt, Matt
AU - Kumamaru, Hiromi
AU - Kawaguchi, Riki
AU - Lu, Paul
AU - Schäfer, Michael K.E.
AU - Woodruff, Grace
AU - Robinson, Jacob
AU - Canete, Philip
AU - Dulin, Jennifer N.
AU - Geoffroy, Cedric G.
AU - Menzel, Lutz
AU - Zheng, Binhai
AU - Coppola, Giovanni
AU - Tuszynski, Mark H.
N1 - Funding Information:
This work was supported by the Veterans Administration, the NIH (grant nos. NS09881 and EB014986; to M.H.T.; and NS054734 to B.Z.), Deutsche Forschungsgemeinschaft (grant no. CRC1080; to L.M. and M.K.E.S.), The Craig H. Neilsen Foundation (to M.H.T.), the Bernard and Anne Spitzer Charitable Trust (to M.H.T.), and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to M.H.T.). We acknowledge the support of the NINDS (National Institute of Neurological Disorders and Stroke) Informatics Center for Neurogenetics and Neurogenomics (grant no. P30 NS062691; to G.C.).
Publisher Copyright:
Copyright © 2018 The Authors, some rights reserved.
PY - 2018/5/23
Y1 - 2018/5/23
N2 - Axon regeneration after spinal cord injury (SCI) is attenuated by growth inhibitory molecules associated with myelin. We report that rat myelin stimulated the growth of axons emerging from rat neural progenitor cells (NPCs) transplanted into sites of SCI in adult rat recipients. When plated on a myelin substrate, neurite outgrowth from rat NPCs and from human induced pluripotent stem cell (iPSC)–derived neural stem cells (NSCs) was enhanced threefold. In vivo, rat NPCs and human iPSC–derived NSCs extended greater numbers of axons through adult central nervous system white matter than through gray matter and preferentially associated with rat host myelin. Mechanistic investigations excluded Nogo receptor signaling as a mediator of stem cell–derived axon growth in response to myelin. Transcriptomic screens of rodent NPCs identified the cell adhesion molecule neuronal growth regulator 1 (Negr1) as one mediator of permissive axon-myelin interactions. The stimulatory effect of myelin-associated proteins on rodent NPCs was developmentally regulated and involved direct activation of the extracellular signal–regulated kinase (ERK). The stimulatory effects of myelin on NPC/NSC axon outgrowth should be investigated further and could potentially be exploited for neural repair after SCI.
AB - Axon regeneration after spinal cord injury (SCI) is attenuated by growth inhibitory molecules associated with myelin. We report that rat myelin stimulated the growth of axons emerging from rat neural progenitor cells (NPCs) transplanted into sites of SCI in adult rat recipients. When plated on a myelin substrate, neurite outgrowth from rat NPCs and from human induced pluripotent stem cell (iPSC)–derived neural stem cells (NSCs) was enhanced threefold. In vivo, rat NPCs and human iPSC–derived NSCs extended greater numbers of axons through adult central nervous system white matter than through gray matter and preferentially associated with rat host myelin. Mechanistic investigations excluded Nogo receptor signaling as a mediator of stem cell–derived axon growth in response to myelin. Transcriptomic screens of rodent NPCs identified the cell adhesion molecule neuronal growth regulator 1 (Negr1) as one mediator of permissive axon-myelin interactions. The stimulatory effect of myelin-associated proteins on rodent NPCs was developmentally regulated and involved direct activation of the extracellular signal–regulated kinase (ERK). The stimulatory effects of myelin on NPC/NSC axon outgrowth should be investigated further and could potentially be exploited for neural repair after SCI.
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U2 - 10.1126/scitranslmed.aal2563
DO - 10.1126/scitranslmed.aal2563
M3 - Article
C2 - 29794059
AN - SCOPUS:85047531521
SN - 1946-6234
VL - 10
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 442
M1 - eaal2563
ER -