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Establishment of induced pluripotent stem cells from aged mice using bone marrow-derived myeloid cells

Journal of Molecular Cell Biology 2011年第2期3卷 91-98页

作者： Zhao Cheng Sachiko Ito Naomi Nishio Hengyi Xiao Rong Zhang Haruhiko Suzuki Yayoi Okawa Toyoaki Murohara Ken-ichi Isobe Department of Immunology Nagoya University Graduate School of Medicine65 Turumai-choShowa-kuNagoyaAichi 466-8520Japan Laboratory for Geriatrics State Key Laboratory of BiotherapySichuan UniversityChengdu 610041China Department of Functioning Activation National Institute for Longevity SciencesNational Center for Geriatrics GerontologyAichi 463-0003Japan Department of Cardiology Nagoya University Graduate School of Medicine65 Turumai-choShowa-kuNagoyaAichi 466-8520Japan

If induced pluripotent stem(iPS)cells are to be used to treat damaged tissues or repair organs in elderly patients,it will be necessary to establish iPS cells from their *** determine the feasibility of using this technology with elderly patients,we asked if it was indeed possible to establish iPS cells from the bone marrow(BM)of aged *** cells from aged C57BL/6 mice carrying the green fluorescence protein(GFP)gene were cultured with granulocyte macrophage-colony stimulating factor(GM-CSF)for 4 *** factors(Oct3/4,Sox2,Klf4 and c-Myc)were introduced into the BM-derived myeloid(BM-M)*** efficiency of generating iPS cells from aged BM cultured in GM-CSF was ***,we succeeded in obtaining BM-M-iPS cells from aged C57BL/6 mice,which carried *** BM-M-iPS cells expressed SSEA-1 and Pou5f1 and were positive for alkaline phosphatase *** iPS cells did make teratoma with three germ layers following injection into syngeneic C57BL/6 mice,and can be differentiated to three germ layers in *** co-culturing with OP9,the BM-M-iPS cells can be differentiated to the myeloid *** differentiated BM-M-iPS cells proliferated well in the presence of GM-CSF,and lost expression of Nanog and Pou5f1,at least in part,due to methylation of their *** the contrary,Tnf and Il1b gene expression was upregulated and their promoters were hypomethylated.

关键词： induced pluripotent stem cells aged mouse bone marrow myeloid cells gene expression methylation chip assay

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