title: Nucleosome Assembly Protein 1-Like 1 (Nap1l1) Regulates the Proliferation of Murine Induced Pluripotent Stem Cells.
abstract: OBJECTIVE
  To investigate whether nucleosome assembly protein 1-like 1 (Nap1l1) regulates the proliferation of induced pluripotent stem cells (iPSC) and the potential mechanisms.
  
  
  METHODS
  Nap1l1-knockdown-iPSC and Nap1l1-overexpression-iPSC were constructed by transfection of lentiviral particles. The proliferation of iPSC was detected by MTT analysis, and cell cycle was analyzed by flow cytometry.
  
  
  RESULTS
  Nap1l1 overexpression promoted iPSC proliferation and induced G2/M transition compared to their control iPSC while Nap1l1-knockdown-iPSC dramatically displayed the reduced proliferation and accumulated G2/M phase cells. Further analysis showed that Nap1l1 overexpression in iPSC increased the expression of cyclin B1, downregulated the expression of p21 and p27, while knockdown of Nap1l1 showed the opposite effects. In addition, overexpression of Nap1l1 promoted the phosphorylation of AKT and ERK in iPSC, while knockdown of Nap1l1 inhibited the effects. However, these effects displayed in Nap1l1-overexpression-iPSC were greatly suppressed by the inhibition of AKT or ERK signaling.
  
  
  CONCLUSIONS
  The results indicate that Nap1l1 promotes the proliferation of iPSC attributable to G2/M transition caused by downregulation of p27 and p21, and upregulation of cyclin B1, the activation of AKT or ERK is involved in the process. The present study has revealed a novel molecular mechanism involved in the proliferation of iPSC.
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yan
authors.forename: Peipei
authors.initials: P
authors.lastname: Yin
authors.forename: Hui
authors.initials: H
authors.lastname: Gong
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xue
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Fang
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Chunjie
authors.initials: C
authors.lastname: Yang
authors.forename: Zheyong
authors.initials: Z
authors.lastname: Huang
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Yang
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D056744:Cyclin B1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D056490:Nucleosome Assembly Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; C533558:Nap1l1 protein, mouse; D056490:Nucleosome Assembly Protein 1; D034741:RNA, Small Interfering; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases