title: Differentiation of human ES cell-derived neural progenitors to neuronal cells with regional specific identity by co-culturing of notochord and somite.
abstract: Limitations to the in vivo study of human nervous system development make it necessary to design an in vitro model to evaluate the in vivo effects of surrounding tissues on neurogenesis and regional identity of the human neural plate. Rostral neural progenitors (NPs) were initially generated from adherent human embryonic stem cells (hESCs) in a defined condition and characterized. Then, to find the role of somites (S) and notochords (N) in rostro-caudal (RC) and dorso-ventral (DV) patterning of neuronal cells, NPs were co-cultured with microencapsulated chicken S or N in alginate beads. In this study, N induced more neurogenesis as evaluated by expression of TUJ1 and MAP2-positive cells. Additionally, N induced spinal cord ventral brachiothoracic identity as well as NPs proliferation. We observed a synergic effect on motoneuron induction when S and N were used together. Moreover, S induced hindbrain identity in differentiated neuronal cells from NPs. These results indicate that highly enriched NPs can be generated in an adherent and defined system from hESCs. Moreover, S and N tissues highly influenced neuronal differentiation in point of proliferation, neurogenesis, and RC and DV regional identity. These results indicate a very simple and efficient protocol to mimic in vivo events of human neural development in vitro which is important in the context of developmental neuroscience and cellular replacement therapies.
authors.affiliation: Department of Cell and Molecular Biology, Cell Science Research Center, Royan Institute for Animal Biotechnology, Esfahan, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Salehi
authors.forename: Khadijeh
authors.initials: K
authors.lastname: Karbalaie
authors.forename: Ahmad
authors.initials: A
authors.lastname: Salamian
authors.forename: Abbas
authors.initials: A
authors.lastname: Kiani
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Razavi
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Nasr-Esfahani
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
mesh_terms: D000818:Animals; D019521:Body Patterning; D002454:Cell Differentiation; D049109:Cell Proliferation; D002642:Chick Embryo; D018920:Coculture Techniques; D053595:Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D008954:Models, Biological; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology*; D009672:Notochord / Q000166:cytology*; D019170:Somites / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors