title: Direct conversion of fibroblasts into neural progenitor-like cells by forced growth into 3D spheres on low attachment surfaces.
abstract: Many stem cells grow into three-dimensional (3D) spheres or colonies, such as neural progenitor cells (NPCs) and embryonic stem cells (ESCs). Sphere morphology helps maintaining the stemness of stem cells. Our previous study demonstrated that forced growth of RT4 and HEK293 cells into 3D sphere on low attachment surface could induce stem cell properties. The close relationship between 3D sphere morphology and stem cell stemness drives us to hypothesize that 3D sphere formation induces fibroblasts reprogramming. The key gene Sox2 for reprogramming fibroblasts into NPCs was found to be overexpressed in 3D sphere cultured mouse fibroblasts. These cells exhibited similar morphological and molecular features to NPCs in vitro, were capable of differentiating into neurons, astrocytes and oligodendrocytes, and could generate long-term expandable neurospheres while maintaining differentiation capability. When engrafted into hippocampus of adult rat brain, the 3D sphere cells differentiated into neural cells. Thus, NPCs can be generated from fibroblasts directly through a physical approach without introducing exogenous reprogramming factors.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Guannan
authors.initials: G
authors.lastname: Su
authors.forename: Yannan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jianshu
authors.initials: J
authors.lastname: Wei
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Xiao
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Guan
authors.forename: Renzhi
authors.initials: R
authors.lastname: Wang
authors.forename: Qun
authors.initials: Q
authors.lastname: Dong
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D058953:Neural Stem Cells / Q000166:cytology*; D017207:Rats, Sprague-Dawley; D018874:Spheroids, Cellular / Q000166:cytology*; D013499:Surface Properties; D013623:Tail