title: Direct conversion of human fibroblasts into neuronal restricted progenitors.
abstract: Neuronal restricted progenitors (NRPs) represent a type of transitional intermediate cells that lie between multipotent neural progenitors and terminal differentiated neurons during neurogenesis. These NRPs have the ability to self-renew and differentiate into neurons, but not into glial cells, which is considered an advantage for cellular therapy of human neurodegenerative diseases. However, difficulty in the extraction of highly purified NRPs from normal nervous tissue prevents further studies and applications. In this study, we report the conversion of human fetal fibroblasts into human induced NRPs (hiNRPs) in 11 days by using just three defined factors: Sox2, c-Myc, and either Brn2 or Brn4. The hiNRPs exhibited distinct neuronal characteristics, including cell morphology, multiple neuronal marker expression, self-renewal capacity, and a genome-wide transcriptional profile. Moreover, hiNRPs were able to differentiate into various terminal neurons with functional membrane properties but not glial cells. Direct generation of hiNRPs from somatic cells will provide a new source of cells for cellular replacement therapy of human neurodegenerative diseases.
authors.affiliation: From the Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Qingjian
authors.initials: Q
authors.lastname: Zou
authors.forename: Quanmei
authors.initials: Q
authors.lastname: Yan
authors.forename: Juan
authors.initials: J
authors.lastname: Zhong
authors.forename: Kepin
authors.initials: K
authors.lastname: Wang
authors.forename: Haitao
authors.initials: H
authors.lastname: Sun
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yi
authors.forename: Liangxue
authors.initials: L
authors.lastname: Lai
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D065150:Cellular Reprogramming; D005347:Fibroblasts / Q000166:cytology*; D020869:Gene Expression Profiling; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000637:transplantation; D009474:Neurons / Q000166:cytology*; D033581:Stem Cell Transplantation; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors
keywords: Brn2; Brn4; Induced Neuronal Restricted Progenitors; Induced Pluripotent Stem (iPS) Cell; Neural Stem Cell; Neurons; Reprogramming; Sox2; Trans-differentiation; Transcription Factors