不同组织来源hiPS与hES的关系

yoke

Persistent Donor Cell Gene Expression among Human Induced Pluripotent Stem Cells Contributes to Differences with Human Embryonic Stem Cells
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Human induced pluripotent stem cells (hiPSCs) generated by de-differentiation of adult somatic cells offer potential solutions for the ethical issues surrounding human embryonic stem cells (hESCs), as well as their immunologic rejection after cellular transplantation. However, although hiPSCs have been described as ‘‘embryonic stem cell-like’’, these cells have a distinct gene expression pattern compared to hESCs, making incomplete reprogramming a potential pitfall. It is unclear to what degree the difference in tissue of origin may contribute to these gene expression differences. To answer these important questions, a careful transcriptional profiling analysis is necessary to investigate the exact reprogramming state of hiPSCs, as well as analysis of the impression, if any, of the tissue of origin on the resulting hiPSCs. In this study, we compare  W$ g! ?* {' Z* l* B( @
the gene profiles of hiPSCs derived from fetal fibroblasts, neonatal fibroblasts, adipose stem cells, and keratinocytes to their
1 g# ~4 E( L& W6 L0 U! w) Hcorresponding donor cells and hESCs. Our analysis elucidates the overall degree of reprogramming within each hiPSC line, as well as the ‘‘distance’’ between each hiPSC line and its donor cell. We further identify genes that have a similar mode of regulation in hiPSCs and their corresponding donor cells compared to hESCs, allowing us to specify core sets of donor genes that continue to be expressed in each hiPSC line. We report that residual gene expression of the donor cell type contributes significantly to the differences among hiPSCs and hESCs, and adds to the incompleteness in reprogramming. Specifically, our analysis reveals that fetal fibroblast-derived hiPSCs are closer to hESCs, followed by adipose, neonatal fibroblast, and keratinocyte-derived hiPSCs.+ |4 T  }, \, w

) K8 V. o) ~3 i$ q6 d% K一篇关于hiPS与hES差异的文章，这种差异是建立在已有的不同组织来源iPS在未分化水平上的芯片结果。
7 E2 ?9 ?! H* w; m. U2 [, b结论1：组织来源的iPS带有组织的“记忆”；
  l) U! H# Y9 `" Y. i, q结论2：fetal组织来源的iPS与hES更接近，keratinocyte来源的相对最远。* {$ p8 c' r& j( ~
讨论：这种在未分化水平上的差异是否会影响分化潜能，是否更容易分化成parental tissue？
9 f, t6 `; J2 n7 a) Q1 z. F/ p5 ~      这种差异本身可能也是由于细胞代数，培养方式（feeder or MG），重编程方式的不同而造成的。# e) G- W, r2 W, c0 O" L

6 m8 o1 q6 \* Z我的思考：分化潜能如何判断，一旦出现问题，这种问题到底是细胞本身的问题（就如同不是每个ｈＥＳ都OK一样，虽然都是分离于blastocyst），还是这个组织来源的问题（某些组织来源的iPS就是很差）？
9 ^+ N$ r3 v- x+ z开放性问题，欢迎大家讨论！！6 S5 w$ D7 _! X2 g7 F$ j& j

% Y: Z' R  P0 B0 V本贴转帖自干细胞论坛版主北羽迦楼 的原创文章
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上海过客

重编程  就是 从 山坡下 返回山顶 。 ( ~  X& \9 B9 {- T& n  e; U
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但是 这个图片模拟的山顶是不是 就是 一定只有一种状态 ，这个现在可能还没有定论吧 。

zhongjunmuzhi

好东西啊

zhongjunmuzhi

感谢！

张也行

恩 二楼说的有道理。& |. \! T- k& O: u
我觉得山中申弥教授的一篇综述里曾经也有过这样的比喻：重编程就像爬山。而不同分化阶段的细胞就像处在不同的山坡上，所以越是距离山顶越近的细胞就越容易被重编程到ES cell-like的状态，但是处于分化末端的细胞（山脚的细胞）则不易被重编程，可能有些组织特有的基因没被沉默，有些ES特有的基因没被活化，所以，很可能终末分化的细胞容易处于incomplete reprogramming 的状态（可能是接近山顶的某个状态），这是不是所谓的组织的烙印呢？. [1 J: @) H9 y9 |: o
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我还有一个问题也想和大家讨论：难道ES细胞就一种状态吗？一些marker就只有表达特定的值才是ES，多一点或者少一点都不是了，ES细胞就没有异质性了吗？就像楼主帖子中说的“分化潜能如何判断”？

chalisha

many thx~

小刀

好感动，昨天向老师汇报课题，他说，所有细胞的iPS都是一样的！我心里不服气，不过没证据。要是早看到我就可以顶他一顶了，呵呵！

iseeyou1210

老板现在哪有时间看文献。

jqm12345

说的好

meng19821013

学习了，谢谢