From marrow to brain: expression of neuronal phenotypes in adult mice.
After intravascular delivery of genetically marked adult mouse bone marrow into lethally irradiated normal adult hosts, donor-derived cells expressing neuronal proteins (neuronal phenotypes) developed in the central nervous system. Flow cytometry revealed a population of donor-derived cells in the brain with characteristics distinct from bone marrow. Confocal microscopy of individual cells showed that hundreds of marrow-derived cells in brain sections expressed gene products typical of neurons (NeuN, 200-kilodalton neurofilament, and class III beta-tubulin) and were able to activate the transcription factor cAMP response element-binding protein (CREB). The generation of neuronal phenotypes in the adult brain 1 to 6 months after an adult bone marrow transplant demonstrates a remarkable plasticity of adult tissues with potential clinical applications.
Brazelton
T R
TR
Department of Molecular Pharmacology, CCSR 4215, 269 Campus Drive, Stanford University, Stanford, CA 94305-5175, USA.
Rossi
F M
FM
Keshet
G I
GI
Blau
H M
HM
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D001921:Brain / Q000166:cytology*; D002454:Cell Differentiation; D048429:Cell Size; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology; D010641:Phenotype; D010766:Phosphorylation
D015415:Biomarkers; D017362:Cyclic AMP Response Element-Binding Protein; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins