Variation in Mesodermal and Hematopoietic Potential of Adult Skin-derived Induced Pluripotent Stem Cell Lines in Mice
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Induced pluripotent stem cells (iPSCs) are a promising tool for regenerative medicine. Use of iPSC lines for future hematotherapy will require examination of their hematopoietic potential. Adult skin fibroblast somatic cells constitute a source of iPSCs that can be accessed clinically without ethical issues. Here, we used different methods to compare mesodermal and hematopoietic potential by embryoid body formation of five iPSC lines established from adult mouse tail-tip fibroblasts (TTFs). We observed variation in proliferation and in expression of genes (Brachyury, Tbx1, Gata1, Klf1, Csf1r) and proteins (Flk1, Ter119 and CD45) among TTF-derived lines. 256H18 iPSCs showed highest proliferation and most efficient differentiation into mesodermal and hematopoietic cells, while expression levels of the pluripotency genes Oct3/4, Sox2, Klf4 and Nanog were lowest among lines analyzed. By contrast, the 212B2 line, transduced with c-Myc, showed lowest proliferation and differentiation potential, although expression levels of Oct3/4, Sox2 and Klf4 were highest. Overall, we find that mesodermal and hematopoietic potential varies among iPSCs from an identical tissue source and that c-Myc expression likely underlies these differences.
KeywordsInduced pluripotent stem cells Tail-tip fibroblasts Embryoid body Mesodermal induction Hematopoietic potential
This work was supported by a grant from the Project for Realization of Regenerative Medicine from the Ministry of Education, Culture, Sports, Science and Technology and by a grant from the BASIS project from the Ministry of Education, Culture, Sports, Science and Technology. T. Inoue and K. Kulkeaw is supported by research fellowships from the Ministry of Education, Culture, Sports, Science and Technology, and from The Tokyo Biochemical Research Foundation, respectively. We thank Dr. Keisuke Okita, Ms. Yuka Horio, Ms. Chiyo Mizuochi and the Research Support Center, Graduate School of Medical Sciences, Kyushu University for technical supports, and Dr. Minetaro Ogawa and Dr. Hiroshi Sakamoto for providing LIF. All iPSCs were kindly provided by Dr. Shinya Yamanaka.
Tomoko Inoue performed the experiments, analyzed data and wrote the manuscript. Kasem Kulkeaw, Satoko Okayama and Kenzaburo Tani performed the experiments. Daisuke Sugiyama designed the experiments and wrote the manuscript.
Conflict of Interest
All disclosures will be published when the manuscript is accepted.
- 15.Era, T., Izumi, N., Hayashi, M., Tada, S., & Nishikawa, S. (2008). Multiple mesoderm subsets give rise to endothelial cells, whereas hematopoietic cells are differentiated only from a restricted subset in embryonic stem cell differentiation culture. Stem Cells, 26, 401–411.PubMedCrossRefGoogle Scholar