The role of NF-κB signaling in the maintenance of pluripotency of human induced pluripotent stem cells

Osamu Takase; Masahiro Yoshikawa; Mana Idei; Junichi Hirahashi; Toshiro Fujita; Tsuyoshi Takato; Takayuki Isagawa; Genta Nagae; Hirofumi Suemori; Hiroyuki Aburatani; Keiichi Hishikawa

doi:10.1371/journal.pone.0056399

The role of NF-κB signaling in the maintenance of pluripotency of human induced pluripotent stem cells

PLoS One. 2013;8(2):e56399. doi: 10.1371/journal.pone.0056399. Epub 2013 Feb 20.

Authors

Osamu Takase¹, Masahiro Yoshikawa, Mana Idei, Junichi Hirahashi, Toshiro Fujita, Tsuyoshi Takato, Takayuki Isagawa, Genta Nagae, Hirofumi Suemori, Hiroyuki Aburatani, Keiichi Hishikawa

Affiliation

¹ Department of Advanced Nephrology and Regenerative Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Abstract

NF-κB signaling plays an essential role in maintaining the undifferentiated state of embryonic stem (ES) cells. However, opposing roles of NF-κB have been reported in mouse and human ES cells, and the role of NF-κB in human induced pluripotent stem (iPS) cells has not yet been clarified. Here, we report the role of NF-κB signaling in maintaining the undifferentiated state of human iPS cells. Compared with differentiated cells, undifferentiated human iPS cells showed an augmentation of NF-κB activity. During differentiation induced by the removal of feeder cells and FGF2, we observed a reduction in NF-κB activity, the expression of the undifferentiation markers Oct3/4 and Nanog, and the up-regulation of the differentiated markers WT-1 and Pax-2. The specific knockdown of NF-κB signaling using p65 siRNA also reduced the expression of Oct3/4 and Nanog and up-regulated WT-1 and Pax-2 but did not change the ES-like colony formation. Our results show that the augmentation of NF-κB signaling maintains the undifferentiated state of human iPS and suggest the importance of this signaling pathway in maintenance of human iPS cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers / metabolism
Cell Differentiation / genetics
Down-Regulation / genetics
Gene Knockdown Techniques
Homeodomain Proteins / metabolism
Humans
Induced Pluripotent Stem Cells / cytology*
Induced Pluripotent Stem Cells / metabolism*
Mice
NF-kappa B / metabolism*
Nanog Homeobox Protein
Octamer Transcription Factor-3 / metabolism
RNA, Small Interfering / metabolism
Signal Transduction*
Transcription Factor RelA / metabolism

Substances

Biomarkers
Homeodomain Proteins
NANOG protein, human
NF-kappa B
Nanog Homeobox Protein
Octamer Transcription Factor-3
RNA, Small Interfering
Transcription Factor RelA

Grants and funding

This work was supported, in part, by Mochida Pharmaceutical Co. Ltd., the Ichiro Kanehara Foundation for Promotion of Medical Sciences and Medical Care, the Daiwa Securities Health Foundation, a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and Health Science Research Grants from the Ministry of Health, Labour and Welfare. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.