title: Variation in mesodermal and hematopoietic potential of adult skin-derived induced pluripotent stem cell lines in mice.
abstract: 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.
authors.affiliation: Department of Hematopoietic Stem Cells, SSP Stem Cell Unit, Kyushu University Faculty of Medical Sciences, Station for Collaborative Research 1 4F, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Inoue
authors.forename: Kasem
authors.initials: K
authors.lastname: Kulkeaw
authors.forename: Satoko
authors.initials: S
authors.lastname: Okayama
authors.forename: Kenzaburo
authors.initials: K
authors.lastname: Tani
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D002452:Cell Count; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D058732:Embryoid Bodies / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D000071317:Nanog Homeobox Protein; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D018398:Homeodomain Proteins; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; C489428:Myc protein, mouse; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse