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toptip: 听Shinya Yamanaka讲故事:通过四个转录因子让体细胞变成全能干细胞
作者:USMedEdu
发表时间:2010-01-19
更新时间:2010-01-19
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发信人: toptip (土翁), 信区: Biology
标 题: 听Shinya Yamanaka同学讲故事
发信站: BBS 未名空间站 (Thu Jan 14 23:01:05 2010, 美东)


Shinya Yamanaka何许人也?就是通过四个转录因子让体细胞变成全能干细胞的大牛。

Shinya Yamanaka今天的讲座是我这几年来在NIH听到的最精彩的讲座。他做讲座是我喜
欢的讲故事的方式,交代了他博后的工作,回日本之后如何引申出干细胞的工作,如何
碰巧建立assay,并通过严格的实验和推理筛选到这四个明星转录因子,之后又介绍了
他实验室关于干细胞癌化的最新进展。数据简明易懂,不太重要让人头晕的图全不show
。中间穿插各种趣事,打趣实验室常见的郁闷,并适时地拿自己的秃头开玩笑。既有宏
观的视野和感悟,也有严格细致的研究线索。观众就在一阵阵笑声中听了一个很有信息量的
讲座。

具体说一下他是怎么发现这四个转录因子的:
他回日本之初曾有一段没有帮手自己养400只老鼠的痛苦经历,并得了一种病叫PAD,
Post America Depression (从美国回去后的沮丧症)。独立建实验室之后还是没有研
究生愿意到他的实验组。为了吸引学生,Shinya Yamanaka提出了一个非常ambitious的
目标:把分化后的细胞逆转成多能干细胞。他的假设是存在maintain干细胞多能性的转
录因子,如果把这些转录因子过表达,可能会实现细胞分化的逆转。
他根据已有的线索找到了24个在干细胞中高表达,而在分化细胞低表达的转录因子。他
把抗G418的基因knock in到其中一个转录因子,建立了一个简便的区分干细胞和分化细
胞的办法。也就是这个knock in老鼠的干细胞因为这个因子高表达,所以是抗G418的,
而分化的细胞却会被G418杀死。
他的一个学生将这24个因子一一转到分化的MEF细胞中(G418敏感),试图筛到抗G418
的克隆,不过实验失败了。这时他的学生提出了一个非常大胆的提议,就是同时把24个
因子转到MEF中。结果就真筛出了几十个抗G418的克隆。那么究竟这24个因子哪些因子
是最重要的呢?他们从这24个因子中每次去掉一个因子再转化,于是就鉴定到了这四个
最重要的因子,去掉其中一个因子都不能产生克隆(其中cmyc不是必需的,但是去掉后
克隆数减少很多)。
于是一个划时代的工作诞生了!

我这个复述非常乏味,他在讲这个发现故事的时候那可是有声有色。本次讲座是NIH的
头亲自host的,有录像。有兴趣的朋友可以直接到 NIH videocast网站去看,免费:http://videocast.nih.gov/PastEvents.asp (找 January 14, 2010的录像,明天应该会available)

--
---判天地之美,析万物之理---

※ 修改:·toptip 於 Jan 14 23:26:41 2010 修改本文·[FROM: 69.139.]
※ 来源:·WWW 未名空间站 海外: mitbbs.com 中国: mitbbs.cn·[FROM: 69.139.]


Shinya Yamanaka
From Wikipedia, the free encyclopedia

http://en.wikipedia.org/wiki/Shinya_Yamanaka#External_links

Shinya Yamanaka Born September 4, 1962
Osaka, Japan
Citizenship Japanese
Fields stem cell research
Institutions Gladstone Institute of Cardiovascular Disease
Alma mater Kobe University
Osaka City University Graduate School
Known for Induced Pluripotent Stem Cells
Notable awards Robert Koch Prize (2008)
Shaw Prize (2008)
Albert Lasker Basic Medical Research Award (2009)
Shinya Yamanaka (山中 伸弥, Yamanaka Shin'ya?) (born on September 4, 1962 in Osaka) is a Japanese physician and stem cell researcher. He serves as a professor at the Institute for Frontier Medical Sciences at Kyoto University, as a senior investigator at the UCSF-affiliated J. David Gladstone Institutes in San Francisco, California, and as a professor of anatomy at University of California, San Francisco (UCSF). He was recently awarded the Lasker award.

Contents [hide]
1 Biography
2 Professional career
3 Recognitions
4 Awards
5 References
6 External links


[edit] Biography
He received his M.D. at Kobe University in 1987 and his Ph.D. at Osaka City University Graduate School in 1993. After this he went through a residency in orthopedic surgery at National Osaka Hospital and a postdoctoral fellowship at the Gladstone Institute of Cardiovascular Disease, San Francisco.

[edit] Professional career
From 1987-1989, Yamanaka was a Resident in orthopedic surgery at the National Osaka Hospital. From 1993-1995, he was a Postdoctoral Fellow at the Gladstone Institute of Cardiovascular Disease, which is affiliated with the University of California, San Francisco. From 1995-1996, he was a staff research investigator at the UCSF-affililated Gladstone Institute of Cardiovascular Disease. From 1996-1999, he was an assistant professor at Osaka City University Medical School. From 1999-2003, he was an associate professor at the Nara Institute of Science and Technology. From 2003-2005, he was a professor at the Nara Institute of Science and Technology. From 2004-present, Shinya Yamanaka has been a professor at the Institute for Frontier Medical Sciences.[1]

In 2006, he and his team generated Induced Pluripotent Stem Cells - pluripotent stem cells from adult mouse fibroblasts. In 2007, he and his team were able to generate Induced Pluripotent Stem Cells from human adult fibroblasts.

[edit] Recognitions
In 2007, Shinya Yamanaka was recognized as a "Person Who Mattered" in the Time Person of the Year edition of Time Magazine.[2] Shinya Yamanaka was also nominated as a 2008 Time 100 Finalist.[3]

[edit] Awards
2007 Meyenburg Cancer Research Award [4][5]
2008 Robert Koch Prize
2008 Shaw Prize in Life Science & Medicine[6][7][8]
2008 Sankyo Takamine Memorial Award[9]
2009 Gairdner Foundation International Award[10]
2009 Albert Lasker Award for Basic Medical Research
[edit] References
^ "Shinya Yamanaka MD., Ph.D.". http://www.frontier.kyoto-u.ac.jp/rc02/kyojuE.html.
^ "Junying Yu, James Thomson and Shinya Yamanaka". http://www.time.com/time/specials/2007/article/0,28804,1690753_1690758_1693587,00.html.
^ "Shinya Yamanaka - The 2008 Time 100 Finalists". http://www.time.com/time/specials/2007/article/0,28804,1725112_1723512_1723571,00.html.
^ "Meyenburg Cancer Research Award 2007 given to Dr. Shinya Yamanaka for the artificial generation of stem cells". http://www.dkfz.de/en/presse/pressemitteilungen/2007/dkfz_pm_07_72_e.php.
^ "Meyenburg Cancer Research Award 2007 for artificial stem cell production". http://www.bio-pro.de/en/region/rhein/magazin/04249/index.html.
^ "Gladstone's Shinya Yamanaka Wins Prestigious Shaw Prize for Stem Cell Discoveries". http://pub.ucsf.edu/today/cache/feature/200806103.html.
^ "Gladstone's Shinya Yamanaka wins prestigious Shaw Prize". http://www.bio-medicine.org/biology-news-1/Gladstones-Shinya-Yamanaka-wins-prestigious-Shaw-Prize-3608-1/.
^ "Professor Shinya Yamanaka Awarded the Shaw Prize". http://www.kyoto-u.ac.jp/en/news_data/h/h1/2008/news7/080617_2.htm.
^ "Professor Shinya Granted Sixth Sankyo Takamine Memorial Award". http://www.icems.kyoto-u.ac.jp/cira/doc/080715_takamine_e.pdf.
^ The 2009 Canada Gairdner Award... › Shinya Yamanaka

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