title: Induction of neuronal markers in bone marrow cells: differential effects of growth factors and patterns of intracellular expression.
abstract: Bone marrow cells (BMC) can be induced to express neuronal phenotypic features in vitro, but the extent to which they can transdifferentiate to mature, functional neurons is uncertain. We examined the effects of different growth factors and combinations thereof on the expression of neuronal marker proteins in cultures of BMC enriched in marrow stromal cells. Patterns of neuronal marker expression varied depending on the growth factor or factors to which BMC cultures were exposed. Cultures treated for up to 5 weeks with epidermal growth factor, fibroblast growth factor-2, retinoic acid, and nerve growth factor displayed neuron-like cellular processes and expressed neuronal markers, including the neuronal nuclear antigen NeuN, microtubule-associated protein 2, tau, synaptophysin, alpha(1A) and alpha(1B) calcium channel subunits, NR2A glutamate receptor subunits, and gamma-aminobutyric acid. However, the intracellular distribution of these markers was distinct from their usual distribution in mature neurons. We conclude that a variety of growth factors can drive BMC toward a neuronal phenotype or phenotypes, but that morphological neuronal features and the ectopic expression of neuronal proteins and neurotransmitters may not equate with the ability to execute normal neuronal functions.
authors.affiliation: Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA.
authors.forename: Kunlin
authors.initials: K
authors.lastname: Jin
authors.forename: Xiao Ou
authors.initials: XO
authors.lastname: Mao
authors.forename: Sophie
authors.initials: S
authors.lastname: Batteur
authors.forename: Yunjuan
authors.initials: Y
authors.lastname: Sun
authors.forename: David A
authors.initials: DA
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006133:Growth Substances / Q000096:biosynthesis* / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D009457:Neuroglia / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D006133:Growth Substances; D009414:Nerve Growth Factors; D016222:Fibroblast Growth Factor 2; D014212:Tretinoin; D004815:Epidermal Growth Factor