The prospective analysis in generation of pluripotency in primordial germ cells
The prospective analysis in generation of pluripotency in primordial germ cells
批准号:
21791527
负责人:
KOSAKA Takeo
金额:
$2.58万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Young Scientists (B)
财政年份:
2009
资助国家:
日本
项目状态:
已结题
起止时间:
2009 至 2010
中文摘要
iPS细胞已经在转录因子Klf 4、Sox 2、Oct 4和c-Myc的异位表达后从体细胞产生。为了阐明iPS技术向多能状态的重编程过程,需要将iPS技术应用于安全的临床应用。为了揭示其详细的机制,高效的重编程实验模型被认为是有效的。我们专注于PGCs,它可以在规定的条件下相对高效和快速地重编程为多能干细胞。通过使用小分子,我们试图改善培养条件。我们估计了表观遗传修饰剂和信号抑制剂。最后,我们发现ERK抑制剂、GSK-β抑制剂和TGF-β 1型受体抑制剂的组合有助于在第10天诱导PGC进入多能状态高达约20%。这种培养条件使得能够使用FACS评估和鉴定细胞群体进展到多能状态。我们分析了基因表达,揭示了多能标记物的未知动态变化。本研究成功地将PGCs高效培养至多能状态,为理解重编程过程提供了一个良好的模型。
英文摘要
iPS cells have been generated from somatic cells following ectopic expression of the transcription factors : Klf4, Sox2, Oct4, and c-Myc. To elucidate the reprogramming process to pluripotent state are needed to apply iPS technology for safe clinical application. In order to uncover the detailed mechanisms, high efficient reprogramming experimental model is thought to be effective. We focused on PGCs, which can be reprogrammed into pluripotent stem cells relatively high efficiently and faster than the other cells under defined conditions. By using small molecules, we tried to improve the culture condition. We estimated epigenetic modifiers and signal inhibitors. Finally, we found that combinations of ERK inhibitors, GSK-βinhibitor, and TGF-βtype-1 receptor inhibitor ontributed to induce PGCs into pluripotent state up to about 20% at day 10. This culture condition enabled to assess and identify the cell population progress to pluripotent state using FACS. We analyzed gene expression and uncovered the unknown dynamic change in pluripotent markers. Our high efficient culture of PGCs to pluripotent state would be a good model to understatd reprogramming process.
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DOI:
--
发表时间:
期刊:
影响因子:
--
作者:
[]
通讯作者:
DOI:
10.1074/jbc.m110.216390
发表时间:
2011-03-25
期刊:
The Journal of biological chemistry
影响因子:
--
作者:
[Nagamatsu G, Kosaka T, Kawasumi M, Kinoshita T, Takubo K, Akiyama H, Sudo T, Kobayashi T, Oya M, Suda T]
通讯作者:
Suda T
Prospective analysis of reprogramming process in primordial germ cells.
原始生殖细胞重编程过程的前瞻性分析。
DOI:
--
发表时间:
2009
期刊:
影响因子:
--
作者:
[小坂威雄, 他5名]
通讯作者:
他5名
始原生殖細胞からの多能性幹細胞分化
从原始生殖细胞分化出多能干细胞
DOI:
--
发表时间:
2011
期刊:
影响因子:
--
作者:
[中村太郎, 他, 宮川信一, Ogino H. and Ochi H., 永松剛・小坂威雄・田久保圭誉・大家基嗣・須田年生]
通讯作者:
永松剛・小坂威雄・田久保圭誉・大家基嗣・須田年生
DOI:
10.1371/journal.pone.0003531
发表时间:
2008
期刊:
PloS one
影响因子:
3.7
作者:
[Durcova-Hills G, Tang F, Doody G, Tooze R, Surani MA]
通讯作者:
Surani MA
共 6 条
Search for biomarkers and novel therapeutic strategies targeting heterogeneity and plasticity in prostate cancer
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批准号:17K11158
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$3.0万
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财政年份:2017
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负责人:KOSAKA Takeo
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依托单位:
A novel strategy of prevention of gastric cancer recurrence-prediction of effect of chemotherapy for potential recurrence after curative operation-
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批准号:19591569
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.83万
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财政年份:2007
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负责人:KOSAKA Takeo
-
依托单位:
海外基金