EasySep™小鼠TIL（CD45）正选试剂盒
产品号 #72592_C
激活素/BMP/TGF-β通路抑制剂；抑制ALK5
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总览
LY364947 是 TGFβ/Activin/NODAL 通路的选择性抑制剂，可抑制 ALK5（IC₅₀ = 59 nM）（Sawyer et al.）。LY364947 对 TGFβRII（IC₅₀ = 400 nM）、p38 MAPK（IC₅₀ = 740 nM）和混合谱系激酶 7（MLK-7；IC₅₀ = 1,400 nM）的抑制效果较差 (Li et al., 2006; Sawyer et al.)。
重编程
·与丙戊酸联合使用，可在转导 OCT4、KLF4 和 c-MYC 的小鼠胚胎成纤维细胞重编程中取代 SOX2（Ichida et al.）。
分化
·阻断人间充质干细胞由机械负荷诱导的软骨形成（Li et al., 2010）。
·恢复缺乏Evi-1转录因子的小鼠主动脉旁胸膜细胞的造血潜能（Sato et al.）。
·削弱人胚胎干细胞 (ES) 的定形内胚层分化能力（Jaremko et al.）。
·阻断 TGF-β 诱导的 NMuMg 乳腺上皮细胞或小鼠 ES 细胞衍生内皮细胞的内皮-间质转化 (Peng et al.; Kokudo et al.)。
癌症研究
·抑制用OP-9基质细胞培养的小鼠和人白血病起始细胞的集落形成能力，并且当与伊马替尼联合使用时，降低慢性髓性白血病小鼠模型的致死率（Naka et al.）。
·在基质侵袭试验中降低MDA-MB-231乳腺癌细胞的侵袭性（Shiou et al.）。
细胞类型
癌细胞及细胞系，软骨细胞，内皮细胞，造血干/祖细胞，乳腺细胞，多能干细胞
种属
人，小鼠，非人灵长类，其它细胞系，大鼠
应用
分化，重编程
研究领域
癌症，干细胞生物学
CAS 编号
396129-53-6
化学式
C₁₇H₁₂N₄
纯度
≥98%
通路
Activin/Nodal/TGFβ
靶点
ALK
产品说明书及文档
请在《产品说明书》中查找相关支持信息和使用说明，或浏览下方更多实验方案。
应用领域
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相关材料与文献
技术资料 (3)
文献 (10)
Regulation of developmental competence and commitment towards the definitive endoderm lineage in human embryonic stem cells. Stem cell research 2013 MAY
Abstract
Human embryonic stem cells (hESCs) can self-renew and become all three germ layers. Nodal/Activin signaling specifies developmental status in hESCs: moderate Nodal/Activin signaling maintains pluripotency, while enhancement and inhibition promote definitive endoderm (DE) and neuroectoderm (NE) development, respectively. However, how modulation of Nodal/Activin signaling influences developmental competence and commitment toward specific lineages is still unclear. Here, we showed that enhancement of Nodal/Activin signaling for 4 days was necessary and sufficient to upregulate DE markers, while it diminished the upregulation of NE markers by inhibition of Nodal/Activin signaling. This suggests that after 4 days of enhanced Nodal/Activin signaling, hESCs are committed to the DE lineage and have lost competence toward the NE lineage. In contrast, inhibition of Nodal/Activin signaling using LY364947 for 2 days was sufficient to impair competence toward the DE lineage, although cells were still able to activate LEFTY1 and NODAL, direct targets of Nodal/Activin signaling. Expression analyses indicated that the levels of pluripotency regulators NANOG and POU5F1 were significantly diminished by 2 days of LY364947 treatment, although the expression of NANOG, but not POU5F1, was restored immediately upon Activin A treatment. Thus, downregulation of POU5F1 coincided with the abrogation of DE competence caused by inhibition of Nodal/Activin signaling.
Mechanical load modulates chondrogenesis of human mesenchymal stem cells through the TGF-beta pathway. Journal of cellular and molecular medicine 2010 JUN
Abstract
This study investigated the effect of mechanical load on human mesenchymal stem cell (hMSC) differentiation under different exogenous transforming growth factor-beta1 (TGF-beta(1)) concentrations (0, 1 or 10 ng/ml).The role of the TGF-beta signalling pathway in this process was also studied. Human MSCs were seeded into fibrin-biodegradable polyurethane scaffolds at a cell density of 5 x 10(6) cells per scaffold and stimulated using our bioreactor. One hour of surface motion superimposed on cyclic compression was applied once a day over seven consecutive days. Scaffolds were analysed for gene expression, DNA content and glycosaminoglycan amount. Addition of TGF-beta(1) in the culture medium was sufficient to induce chondrogenesis of hMSCs. Depending on the TGF-beta(1) concentration of the culture medium, mechanical load stimulated chondrogenesis of hMSCs compared to the unloaded scaffolds, with a much stronger effect on gene expression at lower TGF-beta(1) concentrations. With TGF-beta(1) absent in the culture medium, mechanical load stimulated gene transcripts and protein synthesis of TGF-beta(1) and TGF-beta(3). TGF-beta type I receptor inhibitor LY364947 blocked the up-regulation on TGF-beta(1) and TGF-beta(3) production stimulated by mechanical load, and also blocked the chondrogenesis of hMSCs. Taken together, these findings suggest that mechanical load promotes chondrogenesis of hMSCs through TGF-beta pathway by up-regulating TGF-beta gene expression and protein synthesis.
TGF-beta-FOXO signalling maintains leukaemia-initiating cells in chronic myeloid leukaemia. Nature 2010 FEB
Abstract
Chronic myeloid leukaemia (CML) is caused by a defined genetic abnormality that generates BCR-ABL, a constitutively active tyrosine kinase. It is widely believed that BCR-ABL activates Akt signalling that suppresses the forkhead O transcription factors (FOXO), supporting the proliferation or inhibiting the apoptosis of CML cells. Although the use of the tyrosine kinase inhibitor imatinib is a breakthrough for CML therapy, imatinib does not deplete the leukaemia-initiating cells (LICs) that drive the recurrence of CML. Here, using a syngeneic transplantation system and a CML-like myeloproliferative disease mouse model, we show that Foxo3a has an essential role in the maintenance of CML LICs. We find that cells with nuclear localization of Foxo3a and decreased Akt phosphorylation are enriched in the LIC population. Serial transplantation of LICs generated from Foxo3a(+/+) and Foxo3a(-/-) mice shows that the ability of LICs to cause disease is significantly decreased by Foxo3a deficiency. Furthermore, we find that TGF-beta is a critical regulator of Akt activation in LICs and controls Foxo3a localization. A combination of TGF-beta inhibition, Foxo3a deficiency and imatinib treatment led to efficient depletion of CML in vivo. Furthermore, the treatment of human CML LICs with a TGF-beta inhibitor impaired their colony-forming ability in vitro. Our results demonstrate a critical role for the TGF-beta-FOXO pathway in the maintenance of LICs, and strengthen our understanding of the mechanisms that specifically maintain CML LICs in vivo.
更多信息
| 种属 | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 396129-53-6 |
| Chemical Formula | C₁₇H₁₂N₄ |
| 纯度 | ≥ 98% |
| Target | ALK |
| Pathway | Activin/Nodal/TGFβ |
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