title: LIF-dependent primitive neural stem cells derived from mouse ES cells represent a reversible stage of neural commitment.
abstract: Primitive neural stem cells (NSCs) define an early stage of neural induction, thus provide a model to understand the mechanism that controls initial neural commitment. In this study, we investigated primitive NSCs derived from mouse embryonic stem cells (ESCs). By genome-wide transcriptional profiling, we revealed their unique signature and depicted the molecular changes underlying critical cell fate transitions during early neural induction at a global level. Together with qRT-PCR analysis, our data illustrated that primitive NSCs retained expression of key pluripotency genes Oct4 and Nanog, while exhibiting repression of other pluripotency-related genes Zscan4, Foxp1 and Dusp9 and up-regulation of neural markers Sox1 and Hes1. The early differentiation feature in primitive NSCs was also supported by their intermediate characters on cell cycle profiles. Moreover, re-plating primitive NSCs back to ESC culture condition could reverse them back to ESC stage, as shown by reversible regulation of marker genes, cell cycle profile changes and enhanced embryoid body formation. In addition, our microarray analysis also identified genes differentially expressed in primitive NSCs, and loss-of-function analysis demonstrated that Hes1 and Ccdc141 play important function at this stage, opening up an opportunity to further understand the regulation of early neural commitment.
authors: Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors: Wan-Hong
authors: WH
authors: Tsang
authors: Bin
authors: B
authors: Wang
authors: Wing Ki
authors: WK
authors: Wong
authors: Shuo
authors: S
authors: Shi
authors: Xiao
authors: X
authors: Chen
authors: Xiangjun
authors: X
authors: He
authors: Shen
authors: S
authors: Gu
authors: Jiabiao
authors: J
authors: Hu
authors: Chengdong
authors: C
authors: Wang
authors: Pi-Chu
authors: PC
authors: Liu
authors: Gang
authors: G
authors: Lu
authors: Xiongfong
authors: X
authors: Chen
authors: Hui
authors: H
authors: Zhao
authors: Wai-Sang
authors: WS
authors: Poon
authors: Wai-Yee
authors: WY
authors: Chan
authors: Bo
authors: B
authors: Feng
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D015536:Down-Regulation; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000378:metabolism; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D000071317:Nanog Homeobox Protein; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D054637:Dual-Specificity Phosphatases; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D053605:Leukemia Inhibitory Factor; D000071317:Nanog Homeobox Protein; D009419:Nerve Tissue Proteins; D050814:Octamer Transcription Factor-3; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C555241:CCDC141 protein, mouse; C432917:Foxp1 protein, mouse; C489734:Hes1 protein, mouse; C475540:Nanog protein, mouse; C494174:Pou5f1 protein, mouse; C534888:Zscan4d protein, mouse; C484491:Dusp9 protein, mouse