Exploring the Transcriptional Network regulating ES cell Pluripotency

探索调节 ES 细胞多能性的转录网络

• 批准号: 8098019
• 负责人: Sridhar Rao
• 金额: $ 13.31万
• 依托单位: VERSITI WISCONSIN, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8098019
• 关键词: Affect; Affinity Chromatography; Area; Basic Science; Binding; Biological; Boston; Cancer Center; Clinical; Clinical Medicine; Collaborations; Complex; Data; Development; Disease; Fostering; Gene Expression; Gene Targeting; Generations; Genes; Genetic Engineering; Genetic Transcription; In Vitro; LIF gene; Laboratories; Maintenance; Maps; Mass Spectrum Analysis; Medicine; Methods; Mus; Pathway Analysis; Pathway interactions; Physicians; Play; Property; Proteins; Proteomics; Recording of previous events; Regenerative Medicine; Research; Research Personnel; Research Project Grants; Role; STAT3 gene; Scientist; Signal Transduction; Somatic Cell; Specificity; Systems Biology; Time; Tissues; Training; Transcriptional Regulation; Undifferentiated; Work; Yeasts; abstracting; base; career; embryonic stem cell; genome-wide; improved; insight; member; novel; pluripotency; prevent; programs; protein complex; protein protein interaction; stem cell biology; tool; transcription factor; yeast two hybrid system

DESCRIPTION (provided by applicant): Embryonic Stem cells provide both a unique biological tool for answering developmental questions, but also hold significant clinical promise in the area of regenerative medicine. Murine Embryonic Stem Cells (mESCs), which have existed for almost 25 years, are now being studied extensively for their ability to be maintained in vitro for extended periods of time in a pluripotent state (i.e. able to recreate all the tissues within a mouse). Understanding the mechanisms used to maintain pluripotency may allow for the reprogramming of somatic cells, which opens entirely new treatment options for a variety of diseases. This proposal involves a five-year training plan to foster a career in academic medicine, combining basic science with clinical medicine. This proposal utilizes a combination of stem-cell biology, proteomics, and systems biology to answer questions about mESC pluripotency. It will be performed within the Laboratory of Dr. Stuart Orkin, a leader in the field of stem cell biology who has trained numerous physician scientists. The research project will focus on the transcriptional mechanisms used to maintain mESCs in a pluripotent state. Recent work has shown that a small number of key transcription factors, Nanog, Oct4, and StatS appear to play a key role by regulating a large number of target genes. The mechanisms of transcriptional regulation, which are likely based upon key protein: protein interactions, remains to be elucidated. Initial work has revealed some of the key protein complexes formed in mESCs, although the binary interactions remain to be mapped out. In addition, how these protein: protein interactions occur on a genome-wide scale and affect target gene transcription are currently unknown. For this reason, a systematic yeast two-hybrid approach will be used to first confirm the binary interactions that are used to form these transcriptional complexes. Next, the key complexes formed by STATS will be identified using both new and established proteomics approaches. Lastly, to better understand the protein interactions critical for maintenance of mESCs, multiple yeast two-hybrid screens will be used to generate an "interactome", thereby facilitating a systems biology approach to the problem with significant network analysis. This proposal is ideally performed at the DFCI and CHB in Boston, given the long history of physician-scientist training, but also the unique collaboration with the Center for Cancer Systems Biology. (End of Abstract)

描述（由申请人提供）：

项目成果

The cohesin-associated protein Wapal is required for proper Polycomb-mediated gene silencing.

• DOI: 10.1186/s13072-016-0063-7
• 发表时间: 2016
• 期刊: Epigenetics & chromatin
• 影响因子: 3.9
• 作者: Stelloh C;Reimer MH;Pulakanti K;Blinka S;Peterson J;Pinello L;Jia S;Roumiantsev S;Hessner MJ;Milanovich S;Yuan GC;Rao S
• 通讯作者: Rao S

Embryonic Stem Cells: A Perfect Tool for Studying Mammalian Transcriptional Enhancers.

胚胎干细胞：研究哺乳动物转录增强子的完美工具。

• DOI: 10.4172/2157-7633.s10-007
• 发表时间: 2012
• 期刊: Journal of stem cell research & therapy
• 作者: Rao,Sridhar

IQGAP1: insights into the function of a molecular puppeteer.

IQGAP1：对分子木偶功能的洞察力。

• DOI: 10.1016/j.molimm.2015.02.012
• 发表时间: 2015-06
• 期刊: Molecular immunology
• 影响因子: 3.6
• 作者: Abel AM;Schuldt KM;Rajasekaran K;Hwang D;Riese MJ;Rao S;Thakar MS;Malarkannan S
• 通讯作者: Malarkannan S

Sall4 overexpression blocks murine hematopoiesis in a dose-dependent manner.

• DOI: 10.1016/j.exphem.2014.09.004
• 发表时间: 2015-01
• 期刊: Experimental hematology
• 影响因子: 2.6
• 作者: Milanovich S;Peterson J;Allred J;Stelloh C;Rajasekaran K;Fisher J;Duncan SA;Malarkannan S;Rao S
• 通讯作者: Rao S