2C-08 Human and Mouse Induced Pluripotent Stem Cells Are Differentially Reprogrammed in response to Kinase Inhibitors

Conventional human induced pluripotent stem cells (hiPSCs), reprogrammed from somatic cells by induced expression of Oct4, Sox2, Klf4 and c-Myc (OSKM), are phenotypically different from mouse embryonic stem cells (ESCs). In mouse, culture in N2B27 serum-free 2i media (MEK and GSK3 inhibitors; PD0325...

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Published inGenes & Genetic Systems Vol. 86; no. 6; p. 424
Main Authors HIRANO Kunio, NAGATA Shogo, YAMAGUCHI Shinpei, NAKAGAWA Masato, OKITA Keisuke, KOTERA Hidetoshi, AINSCOUGH Justin, TADA Takashi
Format Journal Article
LanguageJapanese
Published The Genetics Society of Japan 2011
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Summary:Conventional human induced pluripotent stem cells (hiPSCs), reprogrammed from somatic cells by induced expression of Oct4, Sox2, Klf4 and c-Myc (OSKM), are phenotypically different from mouse embryonic stem cells (ESCs). In mouse, culture in N2B27 serum-free 2i media (MEK and GSK3 inhibitors; PD0325901 and CHIR99021) plus LIF (Leukemia inhibitory factor)(2i+LIF medium) enriches for germline competent ESCs. Here we demonstrate that flat-shaped hiPSC colonies can be reprogrammed into bowl-shaped multi-potent stem cells (2i-hiPSCs) using 2i+LIF medium. Mechanical dissociation of 2i-hiPSC colonies enables stable maintenance over long periods. Importantly, gene expression profiling demonstrated that 2i-hiPSCs more closely resemble primitive neural stem cells (PNSCs). Notably, 2i-hiPSCs were generated from conventional hiPSCs, but not hESCs, correlating with observation of neuroectodermal SOX1-positive colonies in conventional hiPSCs, but not hESCs in 2i+LIF medium. Thus, 2i-hiPSCs, which are non-teratoma forming PNSCs, may represent a safe source of cells for neural research and regenerative medicine.
ISSN:1341-7568