title: Role of Jnk1 in development of neural precursors revealed by iPSC modeling.
abstract: Jnk1-deficient mice manifest disrupted anterior commissure formation and loss of axonal and dendritic microtubule integrity. However, the mechanisms and the specific stages underlying the developmental defects remain to be elucidated. Here, we report the generation of Jnk1-deficient (Jnk1 KO) iPSCs from Jnk1 KO mouse tail-tip fibroblasts (TTFs) for modeling the neural disease development. The efficiency in the early induction of iPSCs was higher from Jnk1 KO fibroblasts than that of wild-type (WT) fibroblasts. These Jnk1 KO iPSCs exhibited pluripotent stem cell properties and had the ability of differentiation into general three embryonic germ layers in vitro and in vivo. However, Jnk1 KO iPSCs showed reduced capacity in neural differentiation in the spontaneous differentiation by embryoid body (EB) formation. Notably, by directed lineage differentiation, Jnk1 KO iPSCs specifically exhibited an impaired ability to differentiate into early stage neural precursors. Furthermore, the neuroepitheliums generated from Jnk1 KO iPSCs appeared smaller, indicative of neural stem cell developmental defects, as demonstrated by teratoma tests in vivo. These data suggest that Jnk1 deï¬ciency inhibits the development of neural stem cells/precursors and provide insights to further understanding the complex pathogenic mechanisms of JNK1-related neural diseases.
authors.affiliation: Department of Cell Biology and Genetics, State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology and Genetics, State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Cell Biology and Genetics, State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology and Genetics, State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Fu
authors.affiliation: Department of Cell Biology and Genetics, State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Xia
authors.affiliation: Department of Cell Biology and Genetics, State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Cell Biology and Genetics, State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D004847:Epithelial Cells / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology; D005854:Germ Cells / Q000166:cytology; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology*; D013724:Teratoma / Q000378:metabolism
chemical_list: D048055:Mitogen-Activated Protein Kinase 8
keywords: Jnk1; induced pluripotent stem cells (iPSCs); modeling disease; neural differentiation; neural precursors; Neuroscience