Pluripotent Stem Cells in Development and Disease

发育和疾病中的多能干细胞

• 批准号: 8055259
• 负责人: GERALD SCHATTEN
• 金额: $ 1.11万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2010-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8055259
• 关键词: Address; Biology; Cells; Chimera organism; Clinical Research; Communication; Communities; Complement; Data; Derivation procedure; Development; Disease; Doctor of Philosophy; EG Cell Line; Embryo; Fostering; Foundations; Genomic Imprinting; Germ; Human; Image; In Vitro; Medicine; Molecular; Normalcy; Pluripotent Stem Cells; Pregnancy; Primates; Property; Quality Control; Reproduction; Research; Research Personnel; Research Project Grants; Stem Cell Research; Stem cells; Structure of primordial sex cell; Time; Transplantation; frontier; human embryonic stem cell; imprint; in utero; in vivo; multidisciplinary; nonhuman primate; nuclear transfer; pluripotency; pre-clinical; programs; safety testing; symposium

This Program Project addresses among the most important questions in stem cell medicine and biology through responsible studies on the potentials of pluripotent stem cells from humans (hESC) and nonhuman primates (nhpESC) during development in vitro and in utero, and after transplantation in vivo. Conceptually, the overarching themes are the molecular foundations of ESC and Embryonic Germ [EG] cell properties of Pluripotency, Genomic Imprinting, and Differentiation, under the directions of Gerald Schatten, PhD (PD; Project I PI), Roger Pedersen, PhD (co-PD; Project II PI) and Peter Donovan, PhD (co-PD; Project III PI). Each of the three Research Projects, along with three Technological Cores and an administrative one, address interrelated fundamental and pre-clinical problems. Proj I: "Imaging nhpES cells in vitro, in chimerae, and after transplantation." (G Schatten, PI) investigates the developmental potentials of nhpESC and nhpES derived after nuclear transfer (NTnhpES) by examining chimerae and genomic imprinting. Proj II: "Differentiation and Epigenesis of Pluripotent Stem Cells" (R. Pedersen, PI) examines the earliest postimplantation embryos, pluripotent cells and their progeny for imprint normalcy, and to determine differentiation stability. Proj III: "Derivation and Safety Testing of Non-Human Primate Embryonic Germ Cell Lines" (P. Donovan, PI) investigates primordial germ cells in vivo, derives nhpEG and compares their developmental potentials with ESCs, while ANALYZING genomic imprinting in utero and in vitro during reproduction. Imaging Core A (E. Ahrens, Core Director) non-invasively images in utero development, ESC/EGs in vitro, and tracks transplanted nhp/hESC with specific probes in vivo. Primate Core B (L. Hewitson, CD) provides NHP embryos, maintains pregnancies, evaluates, and performs transplants. ADMIN Core C fosters communication, dissemination, and coordination within this P01 and throughout NIH's stem cell research communities by research planning, real-time data transfer, conferences, and scientific exchanges, as well as our advanced lab course 'Frontiers in Human Embryonic Stem Cell Research.' Stem Cell Core D maintains, preserves, and quality controls new and existing nhpES/EG cell lines, distributing them to the projects and freely to other academic investigators. Complementing NIH's new Stem Cell Centers, our multidisciplinary team will make major contributions towards swiftly and accurately addressing key questions whose answers are the essential foundation for stem cell clinical studies.

这个项目解决了干细胞医学和生物学中最重要的问题 通过对人类（hESC）和非人类多能干细胞潜力的负责任研究， 灵长类动物（nhpESC）在体外和子宫内发育期间，以及体内移植后。从概念上讲， 首要的主题是ESC的分子基础和胚胎生殖[EG]细胞的特性， 多能性、基因组印记和分化，在Gerald Schatten博士的指导下（PD; 项目I PI）、Roger Pedersen博士（共同PD;项目II PI）和Peter Donovan博士（共同PD;项目III PI）。 三个研究项目中的每个项目以及三个技术核心和一个行政核心，沿着，地址 相互关联的基础和临床前问题。项目I：“体外、在嵌合体中、以及 移植后。“（G Schatten，PI）研究了nhpESC和nhpES的发育潜力 通过检查嵌合体和基因组印记，获得核转移后（NTnhpES）。项目二： “多能干细胞的分化和表观遗传”（R。Pedersen，PI）检查植入后最早期 胚胎、多能性细胞及其后代的印记正常性，并确定 分化稳定性项目III：“非人灵长类动物胚胎的衍生和安全性试验 Donovan，PI）研究了体内原始生殖细胞，衍生出nhpEG并比较 他们与胚胎干细胞的发育潜力，同时分析子宫内和体外的基因组印记 在生殖过程中。成像核心A（E. Ahrens，核心主任）子宫内非侵入性成像 在体外，用特异性探针追踪nhp/hESC的生长发育，并在体内追踪移植的nhp/hESC。灵长 核心B（左侧）Hewitson，CD）提供NHP胚胎，维持妊娠，评估和执行 移植ADMIN核心C促进了本P01和P02中的沟通、传播和协调， 通过研究计划、实时数据传输、会议， 和科学交流，以及我们的高级实验室课程“人类胚胎干细胞前沿” Research.干细胞核心D维持，保存和质量控制新的和现有的nhpES/EG细胞 线，分发给项目和免费的其他学术研究人员。补充NIH的新 干细胞中心，我们的多学科团队将作出重大贡献， 解决关键问题，其答案是干细胞临床研究的重要基础。

项目成果

The analysis of mitochondria and mitochondrial DNA in human embryonic stem cells.

• DOI: 10.1385/1-59745-046-4:347
• 发表时间: 2006
• 期刊: Methods in molecular biology
• 作者: J. S. St. John;A. Amaral;E. Bowles;J. F. Oliveira;Rhiannon E. Lloyd;Mariana Freitas;Heather L Gray;C. Navara;Gisela Oliveira;G. Schatten;E. Spikings;J. Ramalho‐Santos

A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints.

• DOI: 10.1016/j.devcel.2008.08.014
• 发表时间: 2008-10
• 期刊: DEVELOPMENTAL CELL
• 影响因子: 11.8
• 作者: Li, Xiajun;Ito, Mitsuteru;Zhou, Fen;Youngson, Neil;Zuo, Xiaopan;Leder, Philip;Ferguson-Smith, Anne C.
• 通讯作者: Ferguson-Smith, Anne C.

Parkinson's Disease: Overview of Transcription Factor Regulation, Genetics, and Cellular and Animal Models.

• DOI: 10.3389/fnins.2022.894620
• 发表时间: 2022
• 期刊: FRONTIERS IN NEUROSCIENCE
• 影响因子: 4.3
• 作者: Xia, Ninuo;Cabin, Deborah E.;Fang, Fang;Reijo Pera, Renee A.
• 通讯作者: Reijo Pera, Renee A.

Energy metabolism in human pluripotent stem cells and their differentiated counterparts.

• DOI: 10.1371/journal.pone.0020914
• 发表时间: 2011
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Varum S;Rodrigues AS;Moura MB;Momcilovic O;Easley CA 4th;Ramalho-Santos J;Van Houten B;Schatten G
• 通讯作者: Schatten G

DNA damage responses in human induced pluripotent stem cells and embryonic stem cells.

• DOI: 10.1371/journal.pone.0013410
• 发表时间: 2010-10-15
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Momcilovic O;Knobloch L;Fornsaglio J;Varum S;Easley C;Schatten G
• 通讯作者: Schatten G