49
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Derivation of Induced Pluripotent Stem Cells from Human Peripheral Blood T Lymphocytes

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Induced pluripotent stem cells (iPSCs) hold enormous potential for the development of personalized in vitro disease models, genomic health analyses, and autologous cell therapy. Here we describe the generation of T lymphocyte-derived iPSCs from small, clinically advantageous volumes of non-mobilized peripheral blood. These T-cell derived iPSCs (“TiPS”) retain a normal karyotype and genetic identity to the donor. They share common characteristics with human embryonic stem cells (hESCs) with respect to morphology, pluripotency-associated marker expression and capacity to generate neurons, cardiomyocytes, and hematopoietic progenitor cells. Additionally, they retain their characteristic T-cell receptor (TCR) gene rearrangements, a property which could be exploited for iPSC clone tracking and T-cell development studies. Reprogramming T-cells procured in a minimally invasive manner can be used to characterize and expand donor specific iPSCs, and control their differentiation into specific lineages.

          Related collections

          Most cited references19

          • Record: found
          • Abstract: found
          • Article: not found

          Human induced pluripotent stem cells free of vector and transgene sequences.

          Reprogramming differentiated human cells to induced pluripotent stem (iPS) cells has applications in basic biology, drug development, and transplantation. Human iPS cell derivation previously required vectors that integrate into the genome, which can create mutations and limit the utility of the cells in both research and clinical applications. We describe the derivation of human iPS cells with the use of nonintegrating episomal vectors. After removal of the episome, iPS cells completely free of vector and transgene sequences are derived that are similar to human embryonic stem (ES) cells in proliferative and developmental potential. These results demonstrate that reprogramming human somatic cells does not require genomic integration or the continued presence of exogenous reprogramming factors and removes one obstacle to the clinical application of human iPS cells.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Suppression of induced pluripotent stem cell generation by the p53-p21 pathway.

            Induced pluripotent stem (iPS) cells can be generated from somatic cells by the introduction of Oct3/4 (also known as Pou5f1), Sox2, Klf4 and c-Myc, in mouse and in human. The efficiency of this process, however, is low. Pluripotency can be induced without c-Myc, but with even lower efficiency. A p53 (also known as TP53 in humans and Trp53 in mice) short-interfering RNA (siRNA) was recently shown to promote human iPS cell generation, but the specificity and mechanisms remain to be determined. Here we report that up to 10% of transduced mouse embryonic fibroblasts lacking p53 became iPS cells, even without the Myc retrovirus. The p53 deletion also promoted the 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. The 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 barrier not only in tumorigenicity, but also in iPS cell generation.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Generation of induced pluripotent stem cells using recombinant proteins.

                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2010
                29 June 2010
                : 5
                : 6
                : e11373
                Affiliations
                [1]Department of Research and Development, Cellular Dynamics International, Inc., Madison, Wisconsin, United States of America
                New York University, United States of America
                Author notes

                Conceived and designed the experiments: MEB ER DR AM RL XF LJZ RDL EFN. Performed the experiments: MEB ER DR RL XF LJZ RDL. Analyzed the data: MEB ER DR RL XF LJZ RDL. Contributed reagents/materials/analysis tools: MEB ER DR AM. Wrote the paper: MEB. Supervised the research project: EFN. Assisted with writing the paper: DR.

                Article
                10-PONE-RA-15577R1
                10.1371/journal.pone.0011373
                2894062
                20617191
                e4177641-b8e4-4b87-84ee-a4615cbefd9e
                Brown et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 15 January 2010
                : 17 May 2010
                Page count
                Pages: 9
                Categories
                Research Article
                Cardiovascular Disorders
                Developmental Biology/Stem Cells
                Immunology/Leukocyte Development
                Neuroscience/Neuronal and Glial Cell Biology
                Hematology/Hematopoiesis

                Uncategorized
                Uncategorized

                Comments

                Comment on this article