Efficient reprogramming of human and mouse primary extra-embryonic cells to pluripotent stem cells

• Published in: Genes to cells : devoted to molecular & cellular mechanisms Vol. 14; no. 12; pp. 1395 - 1404
• Main Authors: Nagata, Shogo, Toyoda, Masashi, Yamaguchi, Shinpei, Hirano, Kunio, Makino, Hatsune, Nishino, Koichiro, Miyagawa, Yoshitaka, Okita, Hajime, Kiyokawa, Nobutaka, Nakagawa, Masato, Yamanaka, Shinya, Akutsu, Hidenori, Umezawa, Akihiro, Tada, Takashi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.12.2009; Blackwell Publishing Ltd
• Subjects: Amnion - cytology; Amnion - metabolism; Animals; Biomarkers - metabolism; Cell Differentiation; Cellular Reprogramming - physiology; Chimera; DNA Methylation; Embryonic Stem Cells - physiology; Female; Gene Expression Profiling; Gene Expression Regulation, Developmental; Humans; Immunoenzyme Techniques; Infant, Newborn; Male; Mice; Mice, Transgenic; Pluripotent Stem Cells - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Teratoma - metabolism; Teratoma - pathology; Yolk Sac - cytology; Yolk Sac - metabolism
• ISSN: 1356-9597; 1365-2443; 1365-2443
• DOI: 10.1111/j.1365-2443.2009.01356.x

Practical clinical applications for current induced pluripotent stem cell (iPSC) technologies are hindered by very low generation efficiencies. Here, we demonstrate that newborn human (h) and mouse (m) extra-embryonic amnion (AM) and yolk-sac (YS) cells, in which endogenous KLF4/Klf4, c-MYC/c-Myc and RONIN/Ronin are expressed, can be reprogrammed to hiPSCs and miPSCs with efficiencies for AM cells of 0.02% and 0.1%, respectively. Both hiPSC and miPSCs are indistinguishable from embryonic stem cells in colony morphology, expression of pluripotency markers, global gene expression profile, DNA methylation status of OCT4 and NANOG, teratoma formation and, in the case of miPSCs, generation of germline transmissible chimeric mice. As copious amounts of human AM cells can be collected without invasion, and stored long term by conventional means without requirement for in vitro culture, they represent an ideal source for cell banking and subsequent 'on demand' generation of hiPSCs for personal regenerative and pharmaceutical applications.