涡虫可用于模拟胚胎干细胞实验

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本周出版的《细胞：干细胞》杂志Reddien与他的实验室同事们开发了一个新方法在涡虫体内识别了控制干细胞行为基因，有趣的是, 这些基因中至少一个类别在人类胚胎干细胞具有对应的副本。& h& s" ?0 b4 V" [8 h8 N

# ^7 V9 ^+ _/ a( Y6 GReddien说：“研究提示涡虫与哺乳动物的干细胞调节方式具有可对比性，这点很有趣。例如,cNeoblasts和胚胎干细胞在分子水平上如何维持功能和干性,可能有相似之处”。2 P. V7 k: i& v$ d3 Q: M& q
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涡虫具有强大的再生能力,并且超过一半的基因与人类同源, 看起来涡虫是研究人类胚胎干细胞一个合乎逻辑的替代选择。
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【涡虫（Planarian）】
4 _9 Q; d+ }0 o9 j5 _# G' r涡虫涡虫大多生活在洁净富氧的海水或淡水中。生活在溪流浅水处的，多隐于石块下面，昼伏夜出。身体柔软，头部具眼点和耳突，体呈树叶形，背腹扁平，腹面密生纤毛，可爬行。全体淡褐色，长10余毫米。4 m' K2 u" P* j3 k1 I' o9 e
涡虫可进行无性生殖，通过横分裂形成子体链，当新个体成熟时从链上脱落，进行独立生活。% O* X. o5 k4 y
涡虫可随着饥饿虫体缩小，退行生长（degrowth），有时从成体大小缩到孵化时的大小，再喂食又能重新生长。推测这种过程可能是组织恢复活力（rejuvenation），胚质不灭（immortality）能力的表现。. e. E. [7 J. u( p. e. ^0 n- T
涡虫强大的再生能力，能再生出身体失去的部分，是一种很好的实验材料，横切为2段或多段，每段均可再生成一完整的涡虫。实质组织是分化新细胞和再生组织的主要来源。
5 y* @- P/ C& ~) @5 V& J/ ?涡虫再生具有极性。如切为3段，前段再生出后端，后段生头，中段前生头后生后端。 : K! B7 f0 x0 O/ d0 S& i3 r. r8 n

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Planarian Genes That Control Stem Cell Biology Identified
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ScienceDaily (Mar. 1, 2012) — Despite their unassuming appearance, the planarian flatworms in Whitehead Institute Member Peter Reddien's lab are revealing powerful new insights into the biology of stem cells -- insights that may eventually help such cells deliver on a promising role in regenerative medicine.$ |* M( Z; o. k7 n- u$ r
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; @# k! s" x) `, B" Q8 l3 g1 aIn this microscope image, an individual stem cell (a cNeoblast) has given rise to colony of cells 14 days after this adult planarian was irradiated. cNeoblast colonies contain multiple types of cells, including both proliferating (red) and differentiating (blue) populations. Quantitative measurements of the sizes and ratios between these cell types provide a new powerful framework for elucidating the roles of stem cell regulatory genes in planarians. (Credit: Dan Wagner/ Whitehead Institute)
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In this week's issue of the journal Cell Stem Cell, Reddien and scientists in his lab report on their development of a novel approach to identify and study the genes that control stem cell behavior in planarians. Intriguingly, at least one class of these genes has a counterpart in human embryonic stem cells.
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8 `8 \4 }& y( r/ l5 l! z2 I9 {+ T4 Y"This is a huge step forward in establishing planarians as an in vivo system for which the roles of stem cell regulators can be dissected," says Reddien, who is also an associate professor of biology at MIT and a Howard Hughes Medical Institute (HHMI) Early Career Scientist. "In the grand scheme of things for understanding stem cell biology, I think this is a beginning foray into seeking general principles that all animals utilize. I'd say we're at the beginning of that process."
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Planarians (Schmidtea mediterranea) are tiny freshwater flatworms with the ability to reproduce through fission. After literally tearing themselves in half, the worms use stem cells, called cNeoblasts, to regrow any missing tissues and organs, ultimately forming two complete planarians in about a week.1 Z0 A3 v: d% S/ ^9 d5 H  _# `; |
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Unlike muscle, nerve, or skin cells that are fully differentiated, certain stem cells, such as cNeoblasts and embryonic stem cells are pluripotent, having the ability to become almost cell type in the body. Researchers have long been interested in harnessing this capability to regrow damaged, diseased, or missing tissues in humans, such as insulin-producing cells for diabetics or nerve cells for patients with spinal cord injuries.) ]( X1 k/ L! u% e: j; q- x1 Y
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Several problems currently confound the therapeutic use of stem cells, including getting the stem cells to differentiate into the desired cell type in the appropriate location and having such cells successfully integrate with surrounding tissues, all without forming tumors. To solve these issues, researchers need a better understanding of how stem cells tick at the molecular level, particularly within the environment of a living organism. To date, a considerable amount of embryonic stem cell research has been conducted in the highly artificial environment of the Petri dish.
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With its renowned powers of regeneration and more than half of its genes having human homologs, the planarian seems like a logical choice for this line of research. Yet, until now, scientists have been unable to efficiently find the genes that regulate the planarian stem cell system.
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. I/ I4 a+ w" L6 X- k. bPostdoctoral researcher Dan Wagner, first author of the Cell Stem Cell paper, and Reddien devised a clever method to identify potential genetic regulators and then determine if those genes affect the two main functions of stem cells: differentiation and renewal of the stem cell population.. F/ Q& e4 O( r5 b& s$ c4 z

  z$ N& K' K* W  \* w' S- g7 i: aAfter identifying genes active in cNeoblasts, Wagner irradiated the planarians, leaving a single surviving cNeoblast in each planarian. Left alone, each cNeoblast can form colonies of new cells at very specific rates of differentiation and stem cell renewal.1 K0 P' D) ?6 p) }' h1 ~9 f5 {
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The researchers knocked down each of the active genes, one per planarian, and observed how the surviving cNeoblasts responded. By comparing the rate of differentiation and stem cell renewal to that of normal cNeoblasts, they could determine the role of each gene. Thus, if a colony containing a certain knocked down gene were observed to have fewer stem cells than the controls, it could be concluded that gene in question plays a role in the process of stem cell renewal. And if the colony had fewer differentiated cells than normal, the knocked down gene could be associated with differentiation.
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"Because it's a quantitative method, we can now precisely measure the role of each gene in different aspects of stem cell function," says Wagner. "Being able to measure stem cell activity with a colony is a great improvement over methods that existed before, which were much more indirect.", P  v" A! N) w# t

$ Y0 |! F! r$ G5 y: i# Z/ K4 cIn total, Wagner identified 10 genes impacting cNeoblast renewal, and two genes with roles in both renewal and differentiation. According to Wagner, three of the stem cell renewal genes are particularly intriguing because they code for proteins that are similar to components of Polycomb Repressive Complex 2 (PRC2), known to regulate stem cell biology in mammalian embryonic stem cells and in other stem cell systems.
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"It's interesting because it suggests a parallel between how stem cells operate in planarians and in mammals. For example, there might be similarities between how cNeoblasts and embryonic stem cells function and maintain stemness at the molecular level," he says.
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8 b5 l2 p7 l5 p& o) e4 z( a0 TThis work was supported by the National Institutes of Health (NIH) and the Keck Foundation.. K7 M% z4 T4 S- y2 q

# e, r; i* I/ ]. M# Ohttp://www.sciencedaily.com/releases/2012/03/120301180912.htm
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% ~9 x/ |3 ^7 ]- m/ F8 Q% ~【扩展阅读】
) f- X3 Z8 X9 l4 y5 g永生的涡虫体细胞可对抗衰老 http://www.stemcell8.cn/thread-52972-1-1.html
" m( X( Z! O: U  I: m  _; M6 {涡虫扁虫：干细胞生物学和神经系统再生的体内模型 http://www.stemcell8.cn/thread-35700-1-1.html
+ U# h2 M3 k; z; M0 A# t英国科学家解开涡虫再生之谜 器官再生有望实现（附原文） http://www.stemcell8.cn/thread-20255-1-1.html
# I1 o/ f6 }( R德国马克斯·普朗克分子生物研究所发现控制涡虫再生能力的“总开关”（附原文） http://www.stemcell8.cn/thread-19052-1-1.html
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