title: Skeletal muscle neural progenitor cells exhibit properties of NG2-glia.
abstract: Reversing brain degeneration and trauma lesions will depend on cell therapy. Our previous work identified neural precursor cells derived from the skeletal muscle of Nestin-GFP transgenic mice, but their identity, origin, and potential survival in the brain are only vaguely understood. In this work, we show that Nestin-GFP+ progenitor cells share morphological and molecular markers with NG2-glia, including NG2, PDGFRα, O4, NGF receptor (p75), glutamate receptor-1(AMPA), and A2B5 expression. Although these cells exhibit NG2, they do not express other pericyte markers, such as α-SMA or connexin-43, and do not differentiate into the muscle lineage. Patch-clamp studies displayed outward potassium currents, probably carried through Kir6.1 channels. Given their potential therapeutic application, we compared their abundance in tissues and concluded that skeletal muscle is the richest source of predifferentiated neural precursor cells. We found that these cells migrate toward the neurogenic subventricular zone displaying their typical morphology and nestin-GFP expression two weeks after brain injection. For translational purposes, we sought to identify these neural progenitor cells in wild-type species by developing a DsRed expression vector under Nestin-Intron II control. This approach revealed them in nonhuman primates and aging rodents throughout the lifespan.
authors.affiliation: Department of Internal Medicine-Gerontology, Wake Forest School of Medicine, Winston Salem, NC 27157, United States.
authors.forename: Alexander
authors.initials: A
authors.lastname: Birbrair
authors.forename: Tan
authors.initials: T
authors.lastname: Zhang
authors.forename: Zhong-Min
authors.initials: ZM
authors.lastname: Wang
authors.forename: María Laura
authors.initials: ML
authors.lastname: Messi
authors.forename: Grigori N
authors.initials: GN
authors.lastname: Enikolopov
authors.forename: Akiva
authors.initials: A
authors.lastname: Mintz
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Delbono
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D000818:Animals; D000941:Antigens / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D005819:Genetic Markers / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000166:cytology* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D064231:Nestin; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D011509:Proteoglycans / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D005819:Genetic Markers; D049452:Green Fluorescent Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; C577485:Nes protein, mouse