Notch Signaling in in vitro derivation of Schwann cells from bone marrow stromal cells

Abstract

Bone marrow stromal cells can be an autologous source of Schwann cells for transplantation to treat demyelination related diseases. Our strategy of deriving Schwann cells from bone marrow stromal cells (Shea et.al, 2010) exploited dorsal root ganglia (DRG) neurons to provide Schwann cell-like cells with juxtacrine signals that mediated commitment to the Schwann cell fate. To address if the juxtacrine signaling is served by Notch and its ligands, analysis of the DRG neurons found cell surface immunopositivities for the ligands, DLL1 and Jagged1 whereas that of bone marrow-derived Schwann cell-like cells found immunopositivity for the receptor, Notch-1. In cocultures with DRG neurons, during which Schwann cell-like cells underwent changes towards fate commitment, the nuclear localization of Notch intracellular domain (NICD) and the expression of downstream target gene hes1 by PCR, were indicative of Notch signaling. This was simultaneous with progressive increase in ErbB2/B3 expression as revealed by immunocytochemistry and Western blotting. Taken together, Notch signaling between DRG neuron and Schwann cell-like cells in contact mediated the upregulation of ErbB receptors in Schwann cell-like cells for signaling interaction with neuregulin as they transition into fate commitment.