Nanog regulates molecules involved in stemness and cell cycle-signaling pathway for maintenance of pluripotency of P19 embryonal carcinoma stem cells

Seung-Cheol Choi, Ji-Hyun Choi, Chi-Yeon Park, Chul-Min Ahn, Soon-Jun Hong, Do-Sun Lim
Journal of Cellular Physiology 2012, 227 (11): 3678-92
To identify potential downstream targets of Nanog, a key transcription factor in the maintenance of pluripotency of embryonic stem (ES) and embryonal carcinoma (EC) cells, global gene expression profiles in Nanog small interfering RNA (siRNA)-transfected P19 EC stem cells were performed using cDNA, 60-mer, and 30-mer microarray platforms. The putative Nanog target genes identified by Nanog silencing were verified using reverse transcription-polymerase chain reaction after Nanog overexpression. Downregulation of Nanog in P19 cells resulted in reduction of pluripotency markers, such as Fgf4, Klf2, Mtf2, Oct-4, Rex1, Sox1, Yes, and Zfp143, whereas overexpression of Nanog in P19 cells reversely upregulated their expression. However, expressions of pluripotency markers Cripto, germ cell nuclear factor, Sox2, and Zfp57 as well as leukemia inhibitory factor (LIF)/Stat3 pathway molecules LIF, IL6st, and Stat3 were not affected after 48 h transfection with Nanog siRNA or construct. Nanog silencing also downregulated expression of molecules involved in the p53- and cell cycle-signaling pathway (Atf3, Jdp2, Cul3, Hist1hic, and Bcl6), whereas expression of E2f1, Tob1, Lyn, and Smarcc1 was upregulated by Nanog silencing. Expressions of cyclins D1, D2, D3, and E1 as well as cyclin-dependent kinase (Cdk) 1 and Cdk6 were downregulated by Nanog silencing in P19 cells, whereas Nanog overexpression reversely increased their expressions. Taken together, examination of global transcriptional changes after Nanog silencing followed by verification by Nanog overexpression has revealed new molecules involved in the maintenance of self-renewal and in the regulation of the p53- and cell cycle-pathway of P19 cells.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"