This article is part of the supplement: Selected articles from the 4th International Conference on Computational Systems Biology (ISB 2010)

Open Access Report

Possible linkages between the inner and outer cellular states of human induced pluripotent stem cells

Shigeru Saito12, Yasuko Onuma3, Yuzuru Ito3, Hiroaki Tateno4, Masashi Toyoda5, Akutsu Hidenori5, Koichiro Nishino5, Emi Chikazawa5, Yoshihiro Fukawatase5, Yoshitaka Miyagawa6, Hajime Okita6, Nobutaka Kiyokawa6, Yohichi Shimma4, Akihiro Umezawa5, Jun Hirabayashi4, Katsuhisa Horimoto17* and Makoto Asashima38*

Author Affiliations

1 Computational Biology Research Center, National Institute of Advanced Industrial Science Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan

2 INFOCOM CORPORATION, Sumitomo Fudosan Harajuku Building, 2-34-17, Jingumae, Shibuya-ku, Tokyo, 150-0001, Japan

3 Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science Technology (AIST), Tsukuba Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562, Japan

4 Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science Technology (AIST), Tsukuba Central 2, 1-1-1 Umezono, Ibaraki 305-8568, Japan

5 Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Ookura, Setagaya-ku, Tokyo 157-8535, Japan

6 Department of Developmental Biology and Pathology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan

7 Institute for Systems Biology, Shanghai University, Shangda Road 99, Shanghai 200444, China

8 Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan

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BMC Systems Biology 2011, 5(Suppl 1):S17  doi:10.1186/1752-0509-5-S1-S17

Published: 20 June 2011



Human iPS cells (hiPSCs) have attracted considerable attention for applications to drug screening and analyses of disease mechanisms, and even as next generation materials for regenerative medicine. Genetic reprogramming of human somatic cells to a pluripotent state was first achieved by the ectopic expression of four factors (Sox2, Oct4, Klf4 and c-Myc), using a retrovirus. Subsequently, this method was applied to various human cells, using different combinations of defined factors. However, the transcription factor-induced acquisition of replication competence and pluripotency raises the question as to how exogenous factors induce changes in the inner and outer cellular states.


We analyzed both the RNA profile, to reveal changes in gene expression, and the glycan profile, to identify changes in glycan structures, between 51 cell samples of four parental somatic cell (SC) lines from amniotic mesodermal, placental artery endothelial, and uterine endometrium sources, fetal lung fibroblast (MRC-5) cells, and nine hiPSC lines that were originally established. The analysis of this information by standard statistical techniques combined with a network approach, named network screening, detected significant expression differences between the iPSCs and the SCs. Subsequent network analysis of the gene expression and glycan signatures revealed that the glycan transfer network is associated with known epitopes for differentiation, e.g., the SSEA epitope family in the glycan biosynthesis pathway, based on the characteristic changes in the cellular surface states of the hiPSCs.


The present study is the first to reveal the relationships between gene expression patterns and cell surface changes in hiPSCs, and reinforces the importance of the cell surface to identify established iPSCs from SCs. In addition, given the variability of iPSCs, which is related to the characteristics of the parental SCs, a glycosyltransferase expression assay might be established to define hiPSCs more precisely and thus facilitate their standardization, which are important steps towards the eventual therapeutic applications of hiPSCs.