Induced pluripotent stem cells (iPSCs) from human patients represent a novel source of cells for regenerative medicine. Because iPSCs can be derived from the tissues of recipient patients, they address two major problems in the field of human embryonic stem cells (hESCs), namely immune rejection and the ethical concerns regarding the destruction of embryos. Understanding the epigenomic states of reprogramming cells will give pivotal insights into the efficiency, safety, and efficacy of iPSCs. To date, the efficiency of iPSC reprogramming is very low at 0.001% to 1%. As iPSC lines are clonal, and derived from a single patient, all cells in differing stages of the transition to iPSC share a common genome. Thus, epigenomic changes underly the reprogramming process. Yet, to date, there have been virtually no studies to explore the epigenomics of the actual reprogramming process itself due to technological difficulties. Novel methods described herein will allow the study of this interval for the first time. First, by use of """"""""biopsies"""""""" with a micropipette, cells of colonies whose fates can be observed prospectively can be procured. Second, an innovative method of amplifying nucleic acids of small numbers of cells allows second generation sequencing technology to be employed. By these methods, the epigenomics changes of colonies can be tracked as they reprogram. The molecular features which are associated with abortive and successful de-differentiation can be defined. Two other topics will be covered in this program project: tissue of origin and aging. Studies to date have shown different tissues de-differentiate at varying efficiencies, and cells of younger subjects are more easily reprogrammed. By understanding the epigenomic landscapes of different tissues and ages and tracking changes during reprogramming, we hope to identify even more features associated with successful and abortive de-differentiation.

Public Health Relevance

Discovering features associated with successful and abortive de-differentiation will form the basis by which reprogramming can be improved, both in efficiency and differentiation potential, by molecular manipulations. This development should bring iPSCs closer for their use in patients for regenerative medicine.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Program Projects (P01)
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Special Emphasis Panel (ZGM1)
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Haynes, Susan R
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Stanford University
Schools of Medicine
United States
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Patterson, Benjamin; Tanaka, Yoshiaki; Park, In-Hyun (2017) New Advances in Human X chromosome status from a Developmental and Stem Cell Biology. Tissue Eng Regen Med 14:643-652
Zhao, Ming-Tao; Shao, Ning-Yi; Hu, Shijun et al. (2017) Cell Type-Specific Chromatin Signatures Underline Regulatory DNA Elements in Human Induced Pluripotent Stem Cells and Somatic Cells. Circ Res 121:1237-1250
Xiang, Yangfei; Tanaka, Yoshiaki; Patterson, Benjamin et al. (2017) Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration. Cell Stem Cell 21:383-398.e7
Zhao, Ming-Tao; Chen, Haodong; Liu, Qing et al. (2017) Molecular and functional resemblance of differentiated cells derived from isogenic human iPSCs and SCNT-derived ESCs. Proc Natl Acad Sci U S A 114:E11111-E11120
Hysolli, Eriona; Tanaka, Yoshiaki; Su, Juan et al. (2016) Regulation of the DNA Methylation Landscape in Human Somatic Cell Reprogramming by the miR-29 Family. Stem Cell Reports 7:43-54
Zhang, Xiaoyan; Marjani, Sadie L; Hu, Zhaoyang et al. (2016) Single-Cell Sequencing for Precise Cancer Research: Progress and Prospects. Cancer Res 76:1305-12
Hu, Shijun; Zhao, Ming-Tao; Jahanbani, Fereshteh et al. (2016) Effects of cellular origin on differentiation of human induced pluripotent stem cell-derived endothelial cells. JCI Insight 1:
Liu, Renjing; Kim, Kun-Yong; Jung, Yong-Wook et al. (2016) Dnmt1 regulates the myogenic lineage specification of muscle stem cells. Sci Rep 6:35355
He, Chunjiang; Hu, Hanyang; Wilson, Kitchener D et al. (2016) Systematic Characterization of Long Noncoding RNAs Reveals the Contrasting Coordination of Cis- and Trans-Molecular Regulation in Human Fetal and Adult Hearts. Circ Cardiovasc Genet 9:110-8
Burridge, Paul W; Diecke, Sebastian; Matsa, Elena et al. (2016) Modeling Cardiovascular Diseases with Patient-Specific Human Pluripotent Stem Cell-Derived Cardiomyocytes. Methods Mol Biol 1353:119-30

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