title: E-cadherin-expressing feeder cells promote neural lineage restriction of human embryonic stem cells.
abstract: Human embryonic stem cells (hESCs) represent a promising source of tissues of different cell lineages because of their high degree of self-renewal and their unique ability to give rise to most somatic cell lineages. In this article, we report on a new approach to differentiate hESCs into neural stem cells that can be differentiated further into neuronal restricted cells. We have rapidly and efficiently differentiated hESCs into neural stem cells by presenting the cell adhesion molecule, E-cadherin, to undifferentiated hESCs via E-cadherin transfected fibroblast monolayers. The neural restricted progenitor cells rapidly express nestin and beta-III-tubulin, but not glial fibrillary acidic protein (GFAP) during the 1-week E-cadherin induction phase, suggesting that E-cadherin promotes rapid neuronal differentiation. Further, these cells are able to achieve enhanced neuronal differentiation with the addition of exogenous growth factors. Cadherin-induced hESCs show a loss in Oct4 and nestin expression associated with positive staining for vimentin, neurofilament, and neural cell adhesion molecule. Moreover, blocking by functional E-cadherin antibody and failure of paracrine stimulation suggested that direct E-cadherin engagement is necessary to induce neural restriction. By providing hESCs with molecular cues to promote differentiation, we are able to utilize a specific cell-cell adhesion molecule, E-cadherin, to influence the nature and degree of neural specialization.
authors.affiliation: Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Rebecca N
authors.initials: RN
authors.lastname: Moore
authors.forename: Jocie F
authors.initials: JF
authors.lastname: Cherry
authors.forename: Vani
authors.initials: V
authors.lastname: Mathur
authors.forename: Rick
authors.initials: R
authors.lastname: Cohen
authors.forename: Martin
authors.initials: M
authors.lastname: Grumet
authors.forename: Prabhas V
authors.initials: PV
authors.lastname: Moghe
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D048430:Cell Shape; D018920:Coculture Techniques; D003598:Cytoskeletal Proteins / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000502:physiology*; D061252:Feeder Cells; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; D015820:Cadherins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins