title: Sequential Differentiation of Embryonic Stem Cells into Neural Epithelial-Like Stem Cells and Oligodendrocyte Progenitor Cells.
abstract: Recent advances in stem cell technology afford an unlimited source of neural progenitors and glial cells for cell based therapy in central nervous system (CNS) disorders. However, current differentiation strategies still need to be improved due to time-consuming processes, poorly defined culture conditions, and low yield of target cell populations.
  
  
  
  This study aimed to provide a precise sequential differentiation to capture two transient stages: neural epithelia-like stem cells (NESCs) and oligodendrocytes progenitor cells (OPCs) derived from mouse embryonic stem cells (ESCs). CHIR99021, a glycogen synthase kinase 3 (GSK-3) inhibitor, in combination with dual SMAD inhibitors, could induce ESCs to rapidly differentiate into neural rosette-like colonies, which facilitated robust generation of NESCs that had a high self-renewal capability and stable neuronal and glial differentiation potentials. Furthermore, SHH combined with FGF-2 and PDGF-AA could induce NESCs to differentiate into highly expandable OPCs. These OPCs not only robustly differentiated into oligodendrocytes, but also displayed an increased migratory activity in vitro.
  
  
  
  We developed a precise and reliable strategy for sequential differentiation to capture NESCs and OPCs derived from ESCs, thus providing unlimited cell source for cell transplantation and drug screening towards CNS repair.
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Collaborative Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Bian
authors.affiliation: Xijing Hospital, The fourth Military Medical University, Xi'an, Shanxi, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Collaborative Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Gerontology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Luo
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Collaborative Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ding
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D051785:Smad Proteins / Q000037:antagonists & inhibitors
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D051785:Smad Proteins; D038362:Glycogen Synthase Kinase 3