Human and mouse induced pluripotent stem cells are differentially reprogrammed in response to kinase inhibitors |
| |
Authors: | Hirano Kunio Nagata Shogo Yamaguchi Shinpei Nakagawa Masato Okita Keisuke Kotera Hidetoshi Ainscough Justin Tada Takashi |
| |
Affiliation: | Laboratory of Stem Cell Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan. |
| |
Abstract: | Conventional human induced pluripotent stem cells (hiPSCs), reprogrammed from somatic cells by induced expression of Oct4, Sox2, Klf4, and c-Myc, are phenotypically different from mouse embryonic stem cells (ESCs). In mice, culture in N2B27 serum-free 2i media (mitogen-activated protein kinase/extracellular signal-regulated kinase and glycogen synthase kinase 3 inhibitors; PD0325901 and CHIR99021) plus leukemia inhibitory factor (LIF) (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) by using 2i+LIF medium. Mechanical dissociation of 2i-hiPSC colonies enables stable maintenance for >20 passages. Importantly, gene expression profiling demonstrated that 2i-hiPSCs more closely resemble primitive neural stem cells (PNSCs). Notably, this 2i-induced phenotype was generated from conventional hiPSCs, but not human ESCs (hESCs), thus correlating with the observation of neuroectodermal SOX1-positive colonies in conventional hiPSCs, but not hESCs in 2i+LIF medium. Thus, 2i-hiPSCs, which are nonteratoma forming PNSCs, may represent a safe source of cells for neural research and regenerative medicine. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|