Probing the mechanism for hydrogel-based stasis induction in human pluripotent stem cells: is the chemical functionality of the hydrogel important?
Probing the mechanism for hydrogel-based stasis induction in human pluripotent stem cells: is the chemical functionality of the hydrogel important?
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DOI：
10.1039/c9sc04734d
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发表时间：
2019-11-11
期刊：
影响因子：
8.4
通讯作者：
Armes SP
中科院分区：
文献类型：
--
作者：
Sponchioni M;O'Brien CT;Borchers C;Wang E;Rivolta MN;Penfold NJW;Canton I;Armes SP
众所周知，多能人类胚胎干细胞（hPSC）可以分化成任何细胞类型。最近，我们报道了 hPSC 集落浸入由羟基功能嵌段共聚物蠕虫组成的极软水凝胶中时进入停滞状态（I. Canton、N. J. Warren、A. Chahal、K. Amps、A. Wood、R. Weightman、E. Wang、H. Moore 和 S. P. Armes，ACS Centr. Sci., 2016, 2, 65–74）。这种合成水凝胶的凝胶模量和化学结构与天然粘蛋白相似，与哺乳动物胚胎的滞育机制有关。停滞诱导的发生仅仅是因为这种水凝胶的非常柔软的性质还是化学功能也发挥了作用？在这里，我们通过设计一种具有相当柔软度的新型水凝胶来解决这个关键问题，其中 PGMA 稳定剂链被非羟基化聚乙二醇 [PEG] 取代。免疫标记研究证实，浸入此类基于 PEG 的水凝胶中的 hPSC 集落不会进入停滞状态，而是会增殖（如果不存在粘附底物，则会进行分化）。然而，如果提供适当的粘附基底，则多能性得以保留。因此，水凝胶的化学功能显然在停滞诱导机制中起着决定性作用。结果表明，需要羟基官能团来诱导浸入具有相当储能模量的全合成嵌段共聚物蠕虫凝胶中的人胚胎干细胞集落的停滞。因此，凝胶柔软度似乎不是停滞诱导的重要参数。
It is well-known that pluripotent human embryonic stem cells (hPSC) can differentiate into any cell type. Recently, we reported that hPSC colonies enter stasis when immersed in an extremely soft hydrogel comprising hydroxyl-functional block copolymer worms (I. Canton, N. J. Warren, A. Chahal, K. Amps, A. Wood, R. Weightman, E. Wang, H. Moore and S. P. Armes, ACS Centr. Sci., 2016, 2, 65–74). The gel modulus and chemical structure of this synthetic hydrogel are similar to that of natural mucins, which are implicated in the mechanism of diapause for mammalian embryos. Does stasis induction occur merely because of the very soft nature of such hydrogels or does chemical functionality also play a role? Herein, we address this key question by designing a new hydrogel of comparable softness in which the PGMA stabilizer chains are replaced with non-hydroxylated poly(ethylene glycol) [PEG]. Immunolabeling studies confirm that hPSC colonies immersed in such PEG-based hydrogels do not enter stasis but instead proliferate (and differentiate if no adhesion substrate is present). However, pluripotency is retained if an appropriate adhesion substrate is provided. Thus, the chemical functionality of the hydrogel clearly plays a decisive role in the stasis induction mechanism. It is shown that hydroxyl functionality is required to induce stasis in human embryonic stem cell colonies immersed within wholly synthetic block copolymer worm gels with comparable storage moduli. Thus gel softness does not appear to be an essential parameter for stasis induction.
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克隆衍生的人类胚胎干细胞系在长期培养过程中保持多能性和增殖潜力
影响因子：
2.7
作者：
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通讯作者：
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影响因子：
18.2
作者：
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影响因子：
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作者：
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影响因子：
3
作者：
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通讯作者：
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DOI：
10.1126/science.1191035
发表时间：
2010-08-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
Blau HM