Several recent studies indicate that tissue-derived stem cells can not only differentiate into cells of the tissue from which they are obtained, but also those from other tissues. We have been interested in the range of differentiative capacity (which we term plasticity) of CNS derived stem cells and hypothesized that one way to assay this would be to implant these cells into blastocyts and assess incorporation into the resulting mice later in development. Our results indicate a robust incorporation of these cells into extraneural tissues including bone marrow, where they express lineage markers of differentiated hematopoietic cells, bone muscle and GI tract. We believe this model provides a unique insight into stem cell plasticity because of the high efficiency of implantation and production of apparently normal pups. We propose to follow-up our studies by addressing the following specific aims: 1) We will determine whether incorporation of stem cells into blastocysts varies as a function of stem cell subpopulation or type, we will create a retorviral library of neural stem cells to assess whether specific subpopulations exist as well as comparing neural stem cells with marrow stromal cells in their ability to incorporate into blastocysts; 2) We will determine whether incorporation of neural stem cells into other tissues renders them functional by performing bone marrow transplantation of cells obtained from chimeric pups into lethally irradiated mice and assessing whether neural stem cells can repair a embryonically lethal genetic defect in bone; and 3) We will assess whether neural stem cells retain their functional capacity to develop into olfactory interneurons after blastocyst transplantation and determine whether their implantation at the blastocyst stage can repair mice with an absence of myelin.
| Ideguchi, Makoto; Palmer, Theo D; Recht, Lawrence D et al. (2010) Murine embryonic stem cell-derived pyramidal neurons integrate into the cerebral cortex and appropriately project axons to subcortical targets. J Neurosci 30:894-904 |
| Low, Hoi Pang; Gréco, Béatrice; Tanahashi, Yusuke et al. (2009) Embryonic stem cell rescue of tremor and ataxia in myelin-deficient shiverer mice. J Neurol Sci 276:133-7 |
| Greco, Beatrice; Low, Hoi Pang; Johnson, Eric C et al. (2004) Differentiation prevents assessment of neural stem cell pluripotency after blastocyst injection. Stem Cells 22:600-8 |
| Li, Li; Liu, Fenghua; Ross, Alonzo H (2003) PTEN regulation of neural development and CNS stem cells. J Cell Biochem 88:24-8 |
| Greco, Beatrice; Recht, Lawrence (2003) Somatic plasticity of neural stem cells: fact or fancy? J Cell Biochem 88:51-6 |
