Abstract
Stage-specific embryonic antigen 1 (SSEA-1) is an antigenic epitope (also called CD15 antigen) defined as a Lewis X carbohydrate structure and known to be expressed in murine embryonal carcinoma cells, mouse embryonic stem cells (ESCs), and murine and human germ cells, but not human ESCs/induced pluripotent stem cells (iPSCs). It is produced by α1,3-fucosyltransferase IX gene (FUT9), and F9 ECCs having a disrupted FUT9 locus by gene targeting are reported to exhibit loss of SSEA-1 expression on their cell surface. Mouse ESCs are pluripotent cells and therefore known as “naïve stem cells (NSCs).” In contrast, human ESCs/iPSCs are thought to be epiblast stem cells (EpiSCs) that are slightly more differentiated than NSCs. Recently, it has been demonstrated that treatment of EpiSCs with several reprograming-related drugs can convert EpiSCs to cells similar to NSCs, which led us to speculate that SSEA-1 may have been expressed in these NSC-like EpiSCs. Immunocytochemical staining of these cells with anti-SSEA-1 revealed increased expression of this epitope. RT-PCR analysis also confirmed increased expression of FUT9 transcripts as well as other stemness-related transcripts such as REX-1 (ZFP42). These results suggest that SSEA-1 can be an excellent marker for human NSCs.
Highlights
Due to the multipotential property of induced pluripotent stem cells, use of these iPSCs and their differentiated derivatives, with respect to regeneration of oral and maxillofacial tissues, is thought to be an important approach in the field of tooth regeneration [1]
Presently available human iPSCs are generally considered to be in a state called “epiblast stem cells (EpiSCs)” that are slightly more differentiated than pluripotential embryonic stem cells (ESCs) called “naïve stem cells (NSCs) or grand-state cells,” as exemplified by murine ESCs [4]
We examined whether human iPSCs, derived from human deciduous tooth dental pulp cells (HDDPCs) [18], begin to express Stage-specific embryonic antigen 1 (SSEA-1) molecules when they are induced to convert to NSCs
Summary
Due to the multipotential property of induced pluripotent stem cells (iPSCs), use of these iPSCs and their differentiated derivatives, with respect to regeneration of oral and maxillofacial tissues, is thought to be an important approach in the field of tooth regeneration [1]. Cai et al [3] describe the generation of tooth-like structures from integration-free human urine-induced pluripotent stem cells (ifhU-iPSCs) They first differentiated ifhU-iPSCs to epithelial sheets, which were recombined with the mouse embryonic dental mesenchyme before transplantation into the mouse subrenal capsule. Presently available human iPSCs are generally considered to be in a state called “epiblast stem cells (EpiSCs)” that are slightly more differentiated than pluripotential embryonic stem cells (ESCs) called “naïve stem cells (NSCs) or grand-state cells,” as exemplified by murine ESCs [4]. SSEA-1 (stage-specific embryonic antigen-1, CD15) is an antigenic epitope [Lewis X: Galβ1-4(Fucα1-3)GlcNAc] that is recognized by a monoclonal antibody (mAb) raised against fixed murine F9 embryonal carcinoma cells (ECCs) that are nullipotent [7] This epitope is expressed in early mouse embryos, and highly undifferentiated cells such as NSC-type of murine ESCs/iPSCs, and germ cells such as primordial germ cells [8,9]. We examined whether human iPSCs, derived from human deciduous tooth dental pulp cells (HDDPCs) [18], begin to express SSEA-1 molecules when they are induced to convert to NSCs
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