Stepwise differentiation of pluripotent stem cells into osteoblasts using four small molecules under serum-free and feeder-free conditions.
Stepwise differentiation of pluripotent stem cells into osteoblasts using four small molecules under serum-free and feeder-free conditions.
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DOI：
10.1016/j.stemcr.2014.04.016
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发表时间：
2014-06-03
影响因子：
5.9
通讯作者：
Ohba, Shinsuke
中科院分区：
文献类型：
--
作者：
Kanke, Kosuke;Masaki, Hideki;Saito, Taku;Komiyama, Yuske;Hojo, Hironori;Nakauchi, Hiromitsu;Lichtler, Alexander C.;Takato, Tsuyoshi;Chung, Ung-il;Ohba, Shinsuke
多能干细胞是一种很有前途的工具，用于组织发育、药物筛选和基于细胞的治疗的机制研究。在这里，我们报告了一个有效的和大量生产的策略，逐步分化的小鼠胚胎干细胞（mESCs）和小鼠和人类诱导多能干细胞（分别为miPSC和hiPSC）进入成骨细胞，使用四种小分子（CHIR 99021 [CHIR]、环巴胺[Cyc]、smoothened激动剂[SAG]和一种向日葵黄素衍生物4-（4-甲氧基苯基）吡啶并[4′，3 ′：4，5]噻吩并[2，3-B]吡啶-2-甲酰胺[TH]）。该策略由中胚层诱导、成骨细胞诱导和成骨细胞成熟阶段组成，显著诱导了mESC、miPSC和hiPSC中成骨细胞相关基因和蛋白的表达。此外，当通过该策略培养缺乏Runx相关转录因子2（Runx 2）（成骨的主要调节因子）的mESC时，它们在分子上重演了Runx 2缺失小鼠的成骨细胞表型。目前的策略将成为成骨细胞发育的生物学和病理学研究、骨增量药物的筛选和骨骼再生的平台。在确定的条件下，成骨细胞从多能干细胞分化。该策略利用四种小分子诱导剂，没有血清或饲养细胞。该策略包括中胚层诱导和随后的成骨细胞诱导。该策略可以至少部分地概括成骨细胞的生理发育。Ohba和同事报告了一种有效的和大量的成骨细胞诱导方法。使用四种小分子逐步分化小鼠胚胎干细胞和小鼠及人诱导多能干细胞为成骨细胞的产生策略（CHIR 99021、环巴胺、SAG和向日葵黄素衍生物）。由中胚层诱导、成骨细胞诱导和成骨细胞成熟阶段组成的策略显著诱导多能干细胞中的成骨细胞形成。
Pluripotent stem cells are a promising tool for mechanistic studies of tissue development, drug screening, and cell-based therapies. Here, we report an effective and mass-producing strategy for the stepwise differentiation of mouse embryonic stem cells (mESCs) and mouse and human induced pluripotent stem cells (miPSCs and hiPSCs, respectively) into osteoblasts using four small molecules (CHIR99021 [CHIR], cyclopamine [Cyc], smoothened agonist [SAG], and a helioxanthin-derivative 4-(4-methoxyphenyl)pyrido[4′,3′:4,5]thieno[2,3-b]pyridine-2-carboxamide [TH]) under serum-free and feeder-free conditions. The strategy, which consists of mesoderm induction, osteoblast induction, and osteoblast maturation phases, significantly induced expressions of osteoblast-related genes and proteins in mESCs, miPSCs, and hiPSCs. In addition, when mESCs defective in runt-related transcription factor 2 (Runx2), a master regulator of osteogenesis, were cultured by the strategy, they molecularly recapitulated osteoblast phenotypes of Runx2 null mice. The present strategy will be a platform for biological and pathological studies of osteoblast development, screening of bone-augmentation drugs, and skeletal regeneration. Osteoblasts were differentiated from pluripotent stem cells under defined conditions The strategy utilizes four small molecule inducers with no serum or feeder cells The strategy comprises mesoderm induction and subsequent osteoblast induction The strategy can at least partially recapitulate physiological osteoblast development Ohba and colleagues report an effective and mass-producing strategy for the stepwise differentiation of mouse embryonic stem cells and mouse and human induced pluripotent stem cells into osteoblasts using four small molecules (CHIR99021, cyclopamine, SAG, and a helioxanthin derivative) under serum-free and feeder-free conditions. The strategy consisting of mesoderm induction, osteoblast induction, and osteoblast maturation phases significantly induced osteoblast formation in pluripotent stem cells.
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影响因子：
2.7
作者：
Tu X;Joeng KS;Long F
通讯作者：
Long F
影响因子：
5.2
作者：
Bilousova, Ganna;Jun, Du Hyun;King, Karen B.;De Langhe, Stijn;Chick, Wallace S.;Torchia, Enrique C.;Chow, Kelsey S.;Klemm, Dwight J.;Roop, Dennis R.;Majka, Susan M.
通讯作者：
Majka, Susan M.
DOI：
10.1073/pnas.0504750102
发表时间：
2005-10-11
影响因子：
11.1
作者：
Akiyama, H;Kim, JE;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
影响因子：
4.1
作者：
Kawaguchi, J;Mee, PJ;Smith, AG
通讯作者：
Smith, AG
影响因子：
5.2
作者：
Plaisant, Magali;Fontaine, Coralie;Peraldi, Pascal
通讯作者：
Peraldi, Pascal