title: Intraspinal transplantation of neurogenin-expressing stem cells generates spinal cord neural progenitors.
abstract: Embryonic stem (ES) cells and their derivatives are an important resource for developing novel cellular therapies for disease. Controlling proliferation and lineage selection, however, are essential to circumvent the possibility of tumor formation and facilitate the safe translation of ES-based therapies to man. Expression of appropriate transcription factors is one approach to direct the differentiation of ES cells towards a specific lineage and stop proliferation. Neural differentiation can be initiated in ES cells by expression of Neurogenin1 (Ngn1). In this study we investigate the effects of controlled Ngn1 expression on mouse ES (mES) cell differentiation in vitro and following grafting into the rat spinal cord. In vitro, Ngn1 expression in mES cells leads to rapid and specific neural differentiation, and a concurrent decrease in proliferation. Similarly transplantation of Ngn1-expressing mES cells into the spinal cord lead to in situ differentiation and spinal precursor formation. These data demonstrate that Ngn1 expression in mES cells is sufficient to promote neural differentiation and inhibit proliferation, thus establishing an approach to safely graft ES cells into the spinal cord.
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: J Simon
authors.initials: JS
authors.lastname: Lunn
authors.forename: Crystal
authors.initials: C
authors.lastname: Pacut
authors.forename: Emily
authors.initials: E
authors.lastname: Stern
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Sakowski
authors.forename: J Matthew
authors.initials: JM
authors.lastname: Velkey
authors.forename: Sue
authors.initials: S
authors.lastname: O'Shea
authors.forename: Eva L
authors.initials: EL
authors.lastname: Feldman
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013118:Spinal Cord Diseases / Q000473:pathology / Q000601:surgery; D033581:Stem Cell Transplantation / Q000379:methods*; D014183:Transplantation, Heterologous / Q000379:methods
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; C486336:Neurog1 protein, mouse