Model systems for studying trophoblast differentiation from human pluripotent stem cells.
Model systems for studying trophoblast differentiation from human pluripotent stem cells.
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DOI：
10.1007/s00441-012-1371-2
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发表时间：
2012-09
影响因子：
3.6
通讯作者：
Roberts, R. Michael
中科院分区：
文献类型：
--
作者：
Ezashi, Toshihiko;Telugu, Bhanu Prakash V. L.;Roberts, R. Michael
本综述重点介绍一种现已成熟的模型，该模型通过用生长因子 BMP4 处理人胚胎干细胞 (ESC) 和诱导多能干细胞 (iPSC) 来生成滋养层 (TB) 谱系细胞。我们首先讨论 FGF2 和 BMP4 在指导 TB 形成中的相反作用，以及将 FGF2 从生长培养基中排除的必要性，以尽量减少中胚层和内胚层的共同诱导。在这些条件下，在 BMP4 暴露后 3 小时内，与结核谱系出现有关的几种转录因子就会上调，并且在几天内，特别是在高氧气气氛下，逐渐出现携带更多分化结核细胞类型标记的细胞类型，包括绒毛外结核和合胞体结核。我们描述了包含阻断激活素 A (INHBA) 和 FGF2 信号传导的低分子量药物以支持 BMP4 定向分化的潜在价值。我们认为，现有证据支持 BMP4 将所谓外胚层类型的人类 ESC 和 iPSC 单向转化为 TB 的论点。我们还认为，在缺乏外源性 FGF2 的情况下，BMP4 处理人 ESC 只会导致中胚层衍生物出现的论点是有严重缺陷的。相反，我们建议，当支持多能性 ESC 或 iPSC 的信号网络变得不可持续，并且当胚胎外中胚层和内胚层的规范变得不起作用时，结核病就会成为多能性的主要默认状态。
This review focuses on a now well-established model for generating cells of the trophoblast (TB) lineage by treating human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) with the growth factor BMP4. We first discuss the opposing roles of FGF2 and BMP4 in directing TB formation and the need to exclude the former from the growth medium to minimize the co-induction of mesoderm and endoderm. Under these conditions, there is up-regulation of several transcription factors implicated in TB lineage emergence within 3 h of BMP4 exposure and, over a period of days and especially under a high O2 gas atmosphere, gradual appearance of cell types carrying markers for more differentiated TB cell types, including extravillous TB and syncytioTB. We describe the potential value of including low molecular weight pharmaceutical agents that block activin A (INHBA) and FGF2 signaling to support BMP4-directed differentiation. We contend that the weight of available evidence supports the contention that BMP4 converts human ESC and iPSC of the so-called epiblast type unidirectionally to TB. We also consider the argument that BMP4 treatment of human ESC in the absence of exogenous FGF2 leads only to the emergence of mesoderm derivatives to be seriously flawed. Instead, we propose that, when signaling networks supporting pluripotency ESC or iPSC become unsustainable and when specification towards extra-embryonic mesoderm and endoderm are rendered inoperative, TB emerges as a major default state to pluripotency.
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影响因子：
3.6
作者：
Ezashi, Toshihiko;Matsuyama, Haruyo;Roberts, R. Michael
通讯作者：
Roberts, R. Michael
影响因子：
64.8
作者：
Brons, I. Gabrielle M.;Smithers, Lucy E.;Vallier, Ludovic
通讯作者：
Vallier, Ludovic
影响因子：
3.8
作者：
Cross, JC
通讯作者：
Cross, JC
影响因子：
3.8
作者：
Aplin, JD;Straszewski-Chavez, SL;Knöfler, M
通讯作者：
Knöfler, M
影响因子：
4
作者：
Alberio, Ramiro;Croxall, Nicola;Allegrucci, Cinzia
通讯作者：
Allegrucci, Cinzia