Glycolipid dynamics in generation and differentiation of induced pluripotent stem cells.

Takuma Ojima,Yoshitaka Miyagawa,Akihiro Umezawa,Shiho Saito,Mayu Yamazaki-Inoue,Hideki Nakajima,Toshinori Sato,Eri Shibata,Jun-Ichiro Fujimoto,Nobutaka Kiyokawa,Masashi Toyoda

doi:10.1038/srep14988

Abstract

Glycosphingolipids (GSLs) are glycoconjugates that function as mediators of cell adhesion and modulators of signal transduction. Some well-defined markers of undifferentiated human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) are glycoconjugates, such as SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81. However, Comprehensive GSL profiles of hiPSCs have not yet been elucidated. The global images of GSLs from the parental cells, hiPSCs, and differentiated cells revealed that there are parental cell-independent specific glycolipids, including Globo H (fucosyl-Gb5Cer) and H type1 antigen (fucosyl-Lc4Cer) that are novel markers for undifferentiated hiPSCs. Interestingly, undifferentiated hiPSCs expressed H type 1 antigen, specific for blood type O, regardless of the cells’ genotypes. Thus, in this study, we defined the dynamics of GSL remodeling during reprogramming from parental cell sets to iPSC sets and thence to iPSC-neural cells.

Highlights

When the technology to generate human iPS cells first became available[1,2], immediate attention was placed on their potential for use in cell-based transplantation
Stem cells have varying degrees of differentiation potential: (a) totipotency, as seen in fertilized eggs; (b) pluripotency, as found in human ESCs (hESCs) and human iPS cells (hiPSCs); (c) multipotentiality, as demonstrated by most tissue-based stem cells; and (d) unipotentiality, as exhibited by epidermal stem cells and the spermatogonial cells of the testis
Since GalCer and galabiose as isomers of GlcCer and LacCer have been detected in hESCs18, existence of other isomers in hiPSCs could not be excluded

Summary

Introduction

When the technology to generate human iPS cells (hiPSCs) first became available[1,2], immediate attention was placed on their potential for use in cell-based transplantation. Both iPSCs (differentiated in vitro) and embryonic stem cells (ESCs) can provide an unlimited source of useful cell types for transplantation. GSLs such as Gb5Cer (SSEA-3), sialyl-Gb5Cer (SSEA-4), fucosyl-Gb5Cer (Globo H), and IV fucosyl-Lc4Cer (H type 1 antigen), have been identified in hESCs. In this study, we investigated the hiPSC-specific GSLs that were induced and highly expressed at the earliest stages of iPSCs generation and down-regulated upon differentiation. We propose that the glycolipid dynamics during generation and differentiation of iPSCs will lead to a better understanding of cellular reprogramming

Methods

Results

Conclusion