Key Molecule for Stem Cell Pluripotency Discovered（附原文）

huangcong1988

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ScienceDaily (May 27, 2011) — Researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch have discovered what enables embryonic stem cells to differentiate into diverse cell types and thus to be pluripotent. This pluripotency depends on a specific molecule -- E-cadherin -- hitherto primarily known for its role in mediating cell-cell adhesion as a kind of "intracellular glue." If E-cadherin is absent, the stem cells lose their pluripotency. The molecule also plays a crucial role in the reprogramming of somatic cells (body cells) into pluripotent stem cells.: q; A3 d% k* A' U' E$ m
Dr. Daniel Besser, Prof. Walter Birchmeier and Torben Redmer from the MDC, a member of the Helmholtz Association, used mouse embryonic fibroblasts (MEFs) in their stem cell experiments. In a first step they showed that the pluripotency of these stem cells is directly associated with the cell-adhesion molecule E-cadherin. If E-cadherin is absent, the stem cells lose their pluripotency. In a second step the researchers investigated what happens when somatic cells that normally neither have E-cadherin nor are pluripotent are reprogrammed into a pluripotent stem cell state. In this reprogramming technique, somatic cells are converted into induced pluripotent stem cells (iPSCs). This new technique may help researchers avoid the controversies that come with the use of human embryos to produce human embryonic stem cells for research purposes.
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/ O4 f& q$ d% K8 w9 Z  ~: lThe MDC researchers found that in contrast to the original cells, the new pluripotent cells derived from mouse connective tissue contained E-cadherin. "Thus, we have double proof that E-cadherin is directly associated with stem-cell pluripotency. E-Cadherin is necessary for maintaining pluripotent stem cells and also for inducing the pluripotent state in the reprogramming of somatic cells," Dr. Besser said. "If E-cadherin is absent, somatic cells cannot be reprogrammed into viable pluripotent cells." In addition, E-Cadherin can replace OCT 4, one of the signaling molecules until now considered indispensable for reprogramming.
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Next, the MDC researchers want to find out to what extent E-cadherin also regulates human embryonic stem cells. "Understanding the molecular relationships is essential for using human somatic cells to develop stem cell therapy for diseases such as heart attack, Alzheimer's or Parkinson's disease or diabetes," Dr. Besser said.
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5 _: P, G- f7 {1 B5 t% i. ^! g5楼原文 感谢zxmflying 提供

林大武

nice

张也行

"E-Cadherin can replace OCT 4, one of the signaling molecules until now considered indispensable for reprogramming"??* T6 X) ]0 p7 A2 v/ ~1 e1 F- ~
真的假的？E-Cadherin在多能性的维持中发挥作用不是什么新鲜事。E-Cadherin对重编程有促进作用也有人研究过，但是E-Cadherin真的能替代Oct4吗？

张也行

E-cadherin is crucial for embryonic stem cell pluripotency and can replace OCT4 during somatic cell reprogramming
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; k0 W& a$ a1 g8 N2 MWe report new functions of the cell-adhesion molecule E-cadherin in murine pluripotent cells. E-cadherin is highly expressed in mouse embryonic stem cells, and interference with E-cadherin causes differentiation. During cellular reprogramming of mouse fibroblasts by OCT4, SOX2, KLF4 and c-MYC, fully reprogrammed cells were exclusively observed in the E-cadherin-positive cell population and could not be obtained in the absence of E-cadherin. Moreover, reprogrammed cells could be established by viral E-cadherin in the absence of exogenous OCT4. Thus, reprogramming requires spatial cues that cross-talk with essential transcription factors. The cell-adhesion molecule E-cadherin has important functions in pluripotency and reprogramming.8 ^+ [& h* P# x* E/ K  R( w
求原文，求真相。http://www.nature.com/embor/jour ... l/embor201188a.html

luoziwei

E-cadherin？它只是细胞表面的一个不可缺少的分子，我觉得一个成功的iPS必须有E-cadherin存在，但说它能替代Oct，确实很新颖，这可能是细胞个体的差异吗？毕竟Oct在胚胎维持中的经典作用已经基本上得到大家的认可了。

zxmflying

原文
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张也行

回复 zxmflying 的帖子+ F4 a; u) f+ V/ b! i0 l. O4 b

0 @" c. y. F7 j  Y0 X十分感谢

huangcong1988

回复 zxmflying 的帖子
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tpwang

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luoziwei 发表于 2011-5-30 15:08 # i/ g7 m, s. J- m1 ~+ U' d3 W0 k
E-cadherin？它只是细胞表面的一个不可缺少的分子，我觉得一个成功的iPS必须有E-cadherin存在，但说它能替代 ...

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这篇文章的结果不是证明E-cadherin取代OCT4在细胞多潜能维持中的作用，而是证明能够取代外源性OCT4在重编程过程中的作用。作者对此现象的解释是，重编程涉及细胞间的空间作用与regulatory factors的相互作用，在这个互相作用中，很可能是E-cadherin的下游机制调控了内源性OCT4。4 Q+ K/ O) H1 x! `( W( I

! v1 {9 a0 f) tSignalling events downstream from E-cadherin might provide a stimulus to upregulate endogenous OCT4. It is tempting to speculate that E-cadherin could control OCT4 through binding and sequestering b-catenin, that is, by modulation of canonical Wnt signalling. 7 k4 L0 ^5 I+ l; J7 q/ d

9 O+ U% U  H5 S2 W2 l这篇文章结果的潜在机制意义是提示细胞多潜能维持以及重编程过程中，通过细胞表面机制与核基因调控的互相作用，细胞之间的空间关系起着重要的作用。这个推论符合常理，因为发育过程中的细胞多潜能状态和分化是在特定空间线索中的自然过程，自然也是研究体外多潜能维持和重编程的重要因素之一吧。
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luoziwei

我也赞同，细胞表面基质直接赋予一个细胞的niche，甚至直接通过filament或者骨架连接到细胞核，从而提供一个外部信号传导。同时，我也猜想，这种传导是很transient的，但是能量却是巨大的。我在哲学课上，曾经听到过一句话，“时间万物都是围绕物质、信息和能量表现的”。“能量”就像“利益”，因此，在我们的课题讨论上，我曾经提出过能量代谢、线粒体在stem cell中的意义，但可惜还得不到有关老师的关注，我很是遗憾。至今，仍然没有找到一种能跟踪细胞瞬时变化的办法，我也在追踪这方面的文献，希望有志者分享。