Induction of a high population of neural stem cells with anterior neuroectoderm characters from epiblast-like P19 embryonic carcinoma cells.
The epiblast, derived from the inner cell mass (ICM), represents the final embryonic founder cell population of mouse embryo and can give rise to all germ layer lineages including the neuroectoderm. The generation of neural stem cells from epiblast-like cells is of great value for studying the mechanism of neural determination during gastrulation stages of embryonic development. Mouse embryonic carcinoma (EC) P19 cells are equivalent to the epiblast of early post-implantation blastocysts. In this study, we establish a feasible induction system that allows rapid and efficient derivation of a high percentage ( approximately 95%) of neural stem cells from P19 EC cell in N2B27 serum-free medium. The induced neural stem cells bear anterior neuroectoderm characters, and can be efficiently caudalized by retinoic acid (RA). These neural stem cells have multilineage potential to differentiate into neurons, astrocytes, and oligodendrocytes. Mechanistic analysis indicates that inhibition of the bone morphogenetic protein (BMP) pathway may be the main reason for N2B27-neural induction, and that fibroblast growth factor (FGF) signaling is also involved in this process. This method will provide an in vitro system to dissect the molecular mechanisms involved in neural induction of early mouse embryos.
Xia
Caihong
C
Laboratory of Molecular Cell Biology, Key Laboratory of Stem Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Wang
Chen
C
Zhang
Kejing
K
Qian
Cheng
C
Jing
Naihe
N
D000818:Animals; D018236:Carcinoma, Embryonal / Q000473:pathology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D019070:Cell Lineage; D002999:Clone Cells; D016895:Culture Media, Serum-Free; D004475:Ectoderm / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology*; D005240:Feasibility Studies; D007150:Immunohistochemistry; D051379:Mice; D009474:Neurons / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D014212:Tretinoin / Q000494:pharmacology
D016895:Culture Media, Serum-Free; D014212:Tretinoin