Induced pluripotent stem (iPS) cells can be generated from somatic cells by introduction of Oct3/4, Sox2, Klf4 and c-Myc, in mouse 1-4 and human [5][6][7][8] . Efficiency of this process, however, is low 9 . Pluripotency can be induced without c-Myc, but with even lower efficiency 10,11 . A p53 siRNA was recently shown to promote human iPS cell generation 12 , but specificity and mechanisms remain to be determined. Here we report that up to 10% of transduced mouse embryonic fibroblasts (MEF) lacking p53 became iPS cells, even without the Myc retrovirus. The p53 deletion also promoted induction of integration-free mouse iPS cells with plasmid transfection. Furthermore, in the p53-null background, iPS cells were generated from terminally differentiated T lymphocytes. Suppression of p53 also increased the efficiency of human iPS cell generation. DNA microarray analyses identified 34 p53-regulated genes that are common in mouse and human fibroblasts. Functional analyses of these genes demonstrate that the p53-p21 pathway serves as a safeguard not only in tumorigenicity, but also in iPS cell generation.We used the Nanog-GFP reporter system for sensitive and specific identification of iPS cells 3 . When the three factors devoid of c-Myc were introduced into Nanog-GFP, p53-wildtype MEF, we obtained 11 ± 8 (n=4) GFP-positive colonies from 5000 transduced fibroblasts ( Figure 1a). From Nanog-GFP, p53-heterozygous mutant MEF, we observed 58 ± 56 GFP-positive colonies. In contrast, from Nanog-GFP, p53-null fibroblasts, we obtained significantly more GFP-positive colonies (275 ± 181) than from wild-type MEF.Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests. Correspondence and requests for materials should be addressed to S.Y. (yamanaka@frontier.kyoto-u.ac.jp).. Author Contributions H.H. conducted most of the experiments in this study. K.T. generated iPS cells from T cells and also performed the shRNA experiments. T.I. performed manipulation of mouse embryos, teratoma experiments, and mouse line maintenance. T. A. and O.K. optimized retroviral transduction into T cells. M.N generated iPS cells with plasmids. K.O. generated the Nanog-GFP reporter mice and the plasmids for iPS cell generation. K.O. and K.T. supervised H.H. S.Y. designed and supervised the study, and prepared the manuscript.Supplementary Information is linked to the online version of the paper at www.nature.com/nature. NIH Public Access Author ManuscriptNature. Author manuscript; available in PMC 2010 August 6. By using a flow cytometer, we plated one Nanog-GFP cell (p53 wild-type, heterozygous mutant, or homozygous mutant), which was transduced with the three factors five days before the re-plating, into a well of 96-well plates. Twenty-three days after the re-plating, we observed GFP-positive colonies in few wells per a 96-well plate with p53 wild-type or heterozygous fibroblasts (Figure 1b). By contrast, we observed GFP-positive colonies in 7 ± 4 (n=4) wells per 96-well ...

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CD2-associated protein (CD2AP) is an 80-kilodalton protein that is critical for stabilizing contacts between T cells and antigen-presenting cells. In CD2AP-deficient mice, immune function was compromised, but the mice died at 6 to 7 weeks of age from renal failure. In the kidney, CD2AP was expressed primarily in glomerular epithelial cells. Knockout mice exhibited defects in epithelial cell foot processes, accompanied by mesangial cell hyperplasia and extracellular matrix deposition. Supporting a role for CD2AP in the specialized cell junction known as the slit diaphragm, CD2AP associated with nephrin, the primary component of the slit diaphragm.

Most of the immunoglobulin A (IgA) in the gut is generated by B cells in the germinal centers of Peyer's patches through a process that requires the presence of CD4+ follicular B helper T(TFH) cells. The nature of these T(FH) cells in Peyer's patches has been elusive. Here, we demonstrate that suppressive Foxp3+CD4+ T cells can differentiate into TFH cells in mouse Peyer's patches. The conversion of Foxp3+ T cells into TFH cells requires the loss of Foxp3 expression and subsequent interaction with B cells. Thus, environmental cues present in gut Peyer's patches promote the selective differentiation of distinct helper T cell subsets, such as TFH cells.