Foxm1 transcription factor is required for maintenance of pluripotency of P19 embryonal carcinoma cells.
Transcription factor Foxm1 plays a critical role during embryonic development and its expression is repressed during retinoic acid (RA)-induced differentiation of pluripotent P19 embryonal carcinoma cells at the early stage, correlated with downregulation of expression of pluripotency markers. To study whether Foxm1 participates in the maintenance of pluripotency of stem cells, we knock down Foxm1 expression in P19 cells and identify that Oct4 are regulated directly by Foxm1. Knockdown of Foxm1 also results in spontaneous differentiation of P19 cells to mesodermal derivatives, such as muscle and adipose tissues. Maintaining Foxm1 expression prevents the downregulation of pluripotency-related transcription factors such as Oct4 and Nanog during P19 cell differentiation. Furthermore, overexpression of FOXM1 alone in RA-differentiated P19 cells (4 days) or human newborn fibroblasts restarts the expression of pluripotent genes Oct4, Nanog and Sox2. Together, our results suggest a critical involvement of Foxm1 in maintenance of stem cell pluripotency.
Xie
Zhongqiu
Z
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Hunan University, Changsha, Hunan 410082, China.
Tan
Guixiang
G
Ding
Miao
M
Dong
Difei
D
Chen
Tuanhui
T
Meng
Xiangxian
X
Huang
Xiaoqin
X
Tan
Yongjun
Y
D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015536:Down-Regulation; D054278:Embryonal Carcinoma Stem Cells / Q000166:cytology* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D007231:Infant, Newborn; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008819:Mice, Nude; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D011401:Promoter Regions, Genetic
D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C491524:Foxm1 protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse