课题基金 / 基金详情

Determinants of Self-Renewal, Differentiation, and Reprogramming of hESCs

Determinants of Self-Renewal, Differentiation, and Reprogramming of hESCs
hESC 自我更新、分化和重编程的决定因素
批准号：
8338841
负责人：
James Alexander Thomson
金额：
$166.1万
依托单位：
MORGRIDGE INSTITUTE FOR RESEARCH, INC.
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
项目状态：
已结题
起止时间：
2008-08-01 至 2014-07-31
来源：
https://reporter.nih.gov/project-details/8338841
关键词：
Cell NucleusCellsCommitDevelopmentEpigenetic ProcessEventGenesHistone CodeHistone H3IndividualLeftLinkMapsMass Spectrum AnalysisMediatingMemoryMyelogenousMyeloid CellsPost-Translational Protein ProcessingProcessProliferatingRegenerative MedicineReportingRoleTechniquesTimeTransactVariantcell typeembryonic stem cellhistone modificationhuman embryonic stem cellnovelnuclear reprogrammingpluripotencypromoterself-renewaltransplantation medicine

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中文摘要
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DESCRIPTION: (provided by applicant): Understanding how human embryonic stem (ES) cells can proliferate without limit and yet retain the ability to differentiate to any cell type is the theme that links the three individual projects of this proposal. Project 1 will identify novel histone modifications in human ES cells using a new mass spectrometry technique that allows an unprecedented ability to identify and map posttranslational protein modifications. Histone modifications in human ES cells will be identified globally, at promoters, and at select genes directly regulated by critical pluripotency factors. We will also examine the role of histone H3 variants in establishing long-term epigenetic memory. These studies will determine whether there is a novel histone code in pluripotent cells and determine how histone modifications change dynamically during differentiation. Project 2 examines the critical events that occur in the window of time during which human ES cells commit eprogram differentiated cells to a pluripotent state. We have previously reported that when myeloid cells are fused with human ES cells, the myeloid nucleus is reprogrammed to an ES cell state, indicating that transacting factors in ES cells are sufficient to mediate nuclear reprogramming. Our preliminary results suggest that over expressing combinations of human ES cell-enriched genes can reprogram myeloid cells, and this project will optimize this reprogramming. The combination of these projects will provide an increased understanding of the pluripotent state and the basic processes by which a cell can leave or return to that state. Such an understanding will be important to transplantation and regenerative medicine. Lay Description: Human ES cells are special because they can grow without limit and can give rise to all other cell types. Here we will try to understand why human ES cells have this remarkable developmental potential, and develop conditions to convert a cell with a more limited potential to an ES cell. Such reprogramming has implications for transplantation and regenerative medicine.
期刊论文(20)
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科研奖励(0)
会议论文
Chemical derivatization of peptide carboxyl groups for highly efficient electron transfer dissociation.
DOI： 10.1007/s13361-013-0701-2
发表时间： 2013-11
期刊： JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
影响因子： 3.2
作者： [Frey, Brian L., Ladror, Daniel T., Sondalle, Samuel B., Krusemark, Casey J., Jue, April L., Coon, Joshua J., Smith, Lloyd M.]
通讯作者： Smith, Lloyd M.
NANOG is multiply phosphorylated and directly modified by ERK2 and CDK1 in vitro.
DOI： 10.1016/j.stemcr.2013.12.005
发表时间： 2014-01-14
期刊： STEM CELL REPORTS
影响因子： 5.9
作者： [Brumbaugh, Justin, Russell, Jason D., Yu, Pengzhi, Westphall, Michael S., Coon, Joshua J., Thomson, James A.]
通讯作者： Thomson, James A.
The Formation and Stability of Alkylthiol Monolayers on Carbon Substrates.
碳基底上烷基硫醇单层的形成和稳定性。
DOI： 10.1021/jp102821x
发表时间： 2010
期刊： The journal of physical chemistry. C, Nanomaterials and interfaces
影响因子： --
作者： [Lockett,MatthewR, Smith,LloydM]
通讯作者： Smith,LloydM
FGF2 sustains NANOG and switches the outcome of BMP4-induced human embryonic stem cell differentiation.
DOI： 10.1016/j.stem.2011.01.001
发表时间： 2011-03-04
期刊： Cell stem cell
影响因子： 23.9
作者： [Yu P, Pan G, Yu J, Thomson JA]
通讯作者： Thomson JA
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