一年一赌：iPS细胞的干性从何而来？

mcherry.f

"另外个人也坚信，总有一天，也许我们并不仅需要化学小分子、蛋白、mRNA、miRNA的诱导来获得iPS细胞，而只要改变培养基的浓度或温度等这些物理或化学条件的改变来成功得到iPS细胞" 4 }& t  T" g  i+ q3 Z6 ?# H8 M
What can be achieved by changing the composition of culture medium can also be achieved by small molecule, protein and RNA, except what you indicated was inorganic compounds/salts.

mcherry.f

回复 marrowstem 的帖子
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Your main point is that iPSCs are from the existing stem cell in cells we used. But there are several lines of evidences against your proposal:
* Z, F; J$ [' \8 ^3 q) q(1) we did not obvious cell death (apoptosis or necrosis) when doing iPSCs.6 j9 }- ?# f. H; H' I! I6 F$ Q
(2) we can observe dramatic epigenetic changing during the early phase of iPSCs production (refers to the recent Cell paper addressing the role of TrxG in ESCs maintenance).
1 R! J7 n) m7 p4 L0 V, K0 J+ ?' D6 uAnd what you pointed out, such as hypoxia, hyperacidic or hyponutrition can induce a quick stress response of cell, but for a long term, such as what we used to produce iPSCs (7dys-14dys for conventional way), your treatment will only lead cell to die. * j" ?9 l& f& h' P2 \
Actually, the mechanism of iPSCs is much clear now. What we do is just to diminish the epigenetic barriers existing in adult cells. And then the several pluripotent factors work to maintain its stemness, either in the way of ground state model or the new proposed precarious model. You can refer to a new article from John Gurdon's group on G & D, and see why even actin contributes to stemness/reprogramming.

mcherry.f

回复 marrowstem 的帖子
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: v7 q% X5 c$ L6 S1, What I indicate is obvious cell death. I don't know whether you know how we calculate the rate of iPSCs? If you just quote it from literature, I suggest to read the methods and materials carefully. Even based on literature, some also said their rate could reach 10% now. Some cells will die definitely, as we culture cells as usual. And there are still bulk of them maintaining the state of MEF or even some intermediate state. How can you indicate that besides the 0.1% other cells are all died?" `4 x* A2 F: o$ k/ S# L. H
2, What I pinpointed are just what you mentioned aforementioned, "缺氧、高酸或缺营养的环境". Can you show the literature that support such conditions can let cell survive for a long term (more than 7dys)? - V" d5 K+ T4 `* k: r) E7 E
3, If your understanding for a biological process just retained on a components clear signaling pathway, I agree with your point that we still know nothing about iPSCs.