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.

[1]  G Cossu,et al.  Muscle regeneration by bone marrow-derived myogenic progenitors. , 1998, Science.

[2]  R. J. Mullen,et al.  NeuN, a neuronal specific nuclear protein in vertebrates. , 1992, Development.

[3]  Snezana Lawrence.  October , 1855, The Hospital.

[4]  A. Vescovi,et al.  Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. , 1999, Science.

[5]  W. Mars,et al.  Bone marrow as a potential source of hepatic oval cells. , 1999, Science.

[6]  D. Wilkin,et al.  Neuron , 2001, Brain Research.

[7]  R. Schutgens.  The metabolic and molecular bases of inherited disease, seventh edition—3-volume set Edited by Charles R. Scriver, Arthur L. Beaudet, William S. Sly, and David Valle. New York, McGraw-Hill, 1995, $285.84 (xxxvi + 4605 pages and 93-page index), ISBN 0-07909-826-6 , 1995, Trends in Endocrinology & Metabolism.

[8]  C. Hillyer.  Turning blood into brain: Cells bearing neuronal antigens generated in vivo from bone marrow , 2001 .

[9]  E. Snyder,et al.  Establishment and Properties of Neural Stem Cell Clones: Plasticity In Vitro and In Vivo , 1999, Brain pathology.

[10]  C. Lois,et al.  Long-distance neuronal migration in the adult mammalian brain. , 1994, Science.

[11]  A. Mccarthy.  Development , 1996, Current Opinion in Neurobiology.

[12]  L. Herzenberg,et al.  Xenogeneic Monoclonal Antibodies to Mouse Lymphoid Differentiation Antigens * , 1979, Immunological reviews.

[13]  F. Gage,et al.  Multipotent progenitor cells in the adult dentate gyrus. , 1998, Journal of neurobiology.

[14]  É. Mezey,et al.  Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. Gurdon,et al.  The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. , 1962, Journal of embryology and experimental morphology.

[16]  F. Gage,et al.  Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[17]  R. Quatrano.  Genomics , 1998, Plant Cell.

[18]  W. Wright.  Expression of differentiated functions in heterokaryons between skeletal myocytes, adrenal cells, fibroblasts and glial cells. , 1984, Experimental cell research.

[19]  F. Gage,et al.  Neurogenesis in the adult human hippocampus , 1998, Nature Medicine.

[20]  A. Shaywitz,et al.  CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. , 1999, Annual review of biochemistry.

[21]  B T Volpe,et al.  Unique Regulation of Immediate Early Gene and Tyrosine Hydroxylase Expression in the Odor-deprived Mouse Olfactory Bulb* , 1999, The Journal of Biological Chemistry.

[22]  G. Galfré,et al.  Monoclonal xenogeneic antibodies to murine cell surface antigens: identification of novel leukocyte differentiation antigens , 1978, European journal of immunology.

[23]  Tomoko Nakanishi,et al.  ‘Green mice’ as a source of ubiquitous green cells , 1997, FEBS letters.

[24]  K. Tamura,et al.  Metabolic engineering of plant alkaloid biosynthesis. Proc Natl Acad Sci U S A , 2001 .

[25]  S. Tilghman,et al.  Role of alpha-fetoprotein regulatory elements in transcriptional activation in transient heterokaryons , 1990, Molecular and cellular biology.

[26]  I. Wilmut,et al.  "Viable Offspring Derived from Fetal and Adult Mammalian Cells" (1997), by Ian Wilmut et al. , 2014 .

[27]  G. Shepherd.  Synaptic organization of the mammalian olfactory bulb. , 1972, Physiological reviews.

[28]  J. Hinds.  Autoradiographic study of histogenesis in the mouse olfactory bulb I. Time of origin of neurons and neuroglia , 1968, The Journal of comparative neurology.

[29]  R. Mulligan,et al.  Dystrophin expression in the mdx mouse restored by stem cell transplantation , 1999, Nature.

[30]  Helen M. Blau,et al.  Cytoplasmic activation of human nuclear genes in stable heterocaryons , 1983, Cell.

[31]  Maria B. Luskin,et al.  Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone , 1993, Neuron.

[32]  I. Black,et al.  Adult rat and human bone marrow stromal cells differentiate into neurons , 2000, Journal of neuroscience research.

[33]  H. Blau,et al.  Differentiation requires continuous regulation , 1991, The Journal of cell biology.

[34]  F. Young.  Biochemistry , 1955, The Indian Medical Gazette.

[35]  P. Mcgeer,et al.  Brain microglia constitutively express β-2 integrins , 1990, Journal of Neuroimmunology.

[36]  K. Deisseroth,et al.  Signaling from Synapse to Nucleus: Postsynaptic CREB Phosphorylation during Multiple Forms of Hippocampal Synaptic Plasticity , 1996, Neuron.