EasySep™小鼠TIL（CD45）正选试剂盒
产品号 #72222_C
p38 MAPK抑制剂
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总览
SB203580（盐酸盐）是p38 MAPK活性的强效抑制剂（IC₅₀ = 0.6 µM）。它可抑制 p38 MAPK 的α和β同工酶，但不抑制 ERK 或 JNK。（Bain et al., Cuenda et al.）
维持和自我更新
·增强小鼠胚胎干细胞（ES）的生长和自我更新（Qi et al.）。
·促进人 naïve ground state 多能干细胞的长期维持（Gafni et al.）。
·促进人内皮祖细胞的增殖（Seeger et al.）。
·促进新生和成年大鼠心肌细胞的增殖（Seeger et al.）。
分化
·增强人 ES 细胞向心肌细胞的分化（Gaur et al., Graichen et al.）。
·通过抑制早期中胚层来抑制小鼠 ES 细胞向心肌细胞的分化（Davidson and Morange）。
别名
PB 203580，RWJ 64809
细胞类型
心肌细胞，PSC衍生，内皮细胞，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，扩增，培养
研究领域
干细胞生物学
CAS 编号
869185-85-3
化学式
C₂₁H₁₆FN₃OS · HCl
分子量
413.9 克/摩尔
纯度
≥ 95 %
通路
p38 MAPK
靶点
p38 MAPK
产品说明书及文档
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应用领域
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相关材料与文献
技术资料 (4)
文献 (9)
Derivation of novel human ground state naive pluripotent stem cells. Nature 2013 DEC
Abstract
Mouse embryonic stem (ES) cells are isolated from the inner cell mass of blastocysts, and can be preserved in vitro in a naive inner-cell-mass-like configuration by providing exogenous stimulation with leukaemia inhibitory factor (LIF) and small molecule inhibition of ERK1/ERK2 and GSK3β signalling (termed 2i/LIF conditions). Hallmarks of naive pluripotency include driving Oct4 (also known as Pou5f1) transcription by its distal enhancer, retaining a pre-inactivation X chromosome state, and global reduction in DNA methylation and in H3K27me3 repressive chromatin mark deposition on developmental regulatory gene promoters. Upon withdrawal of 2i/LIF, naive mouse ES cells can drift towards a primed pluripotent state resembling that of the post-implantation epiblast. Although human ES cells share several molecular features with naive mouse ES cells, they also share a variety of epigenetic properties with primed murine epiblast stem cells (EpiSCs). These include predominant use of the proximal enhancer element to maintain OCT4 expression, pronounced tendency for X chromosome inactivation in most female human ES cells, increase in DNA methylation and prominent deposition of H3K27me3 and bivalent domain acquisition on lineage regulatory genes. The feasibility of establishing human ground state naive pluripotency in vitro with equivalent molecular and functional features to those characterized in mouse ES cells remains to be defined. Here we establish defined conditions that facilitate the derivation of genetically unmodified human naive pluripotent stem cells from already established primed human ES cells, from somatic cells through induced pluripotent stem (iPS) cell reprogramming or directly from blastocysts. The novel naive pluripotent cells validated herein retain molecular characteristics and functional properties that are highly similar to mouse naive ES cells, and distinct from conventional primed human pluripotent cells. This includes competence in the generation of cross-species chimaeric mouse embryos that underwent organogenesis following microinjection of human naive iPS cells into mouse morulas. Collectively, our findings establish new avenues for regenerative medicine, patient-specific iPS cell disease modelling and the study of early human development in vitro and in vivo.
Timed inhibition of p38MAPK directs accelerated differentiation of human embryonic stem cells into cardiomyocytes. Cytotherapy 2010 OCT
Abstract
BACKGROUND AIMS Heart failure therapy with human embryonic stem cell (hESC)-derived cardiomyocytes (hCM) has been limited by the low rate of spontaneous hCM differentiation. As others have shown that p38 mitogen-activated protein kinase (p38MAPK) directs neurogenesis from mouse embryonic stem cells, we investigated whether the p38MAPK inhibitor, SB203580, might influence hCM differentiation. METHODS We treated differentiating hESC with SB203580 at specific time-points, and used flow cytometry, immunocytochemistry, quantitative real-time (RT)-polymerase chain reaction (PCR), teratoma formation and transmission electron microscopy to evaluate cardiomyocyte formation. RESULTS We observed that the addition of inhibitor resulted in 2.1-fold enrichment of spontaneously beating human embryoid bodies (hEB) at 21 days of differentiation, and that 25% of treated cells expressed cardiac-specific α-myosin heavy chain. This effect was dependent on the stage of differentiation at which the inhibitor was introduced. Immunostaining and teratoma formation assays demonstrated that the inhibitor did not affect hESC pluripotency; however, treated hESC gave rise to hCM exhibiting increased expression of sarcomeric proteins, including cardiac troponin T, myosin light chain and α-myosin heavy chain. This was consistent with significantly increased numbers of myofibrillar bundles and the appearance of nascent Z-bodies at earlier time-points in treated hCM. Treated hEB also demonstrated a normal karyotype by array comparative genomic hybridization and viability in vivo following injection into mouse myocardium. CONCLUSIONS These studies demonstrate that p38MAPK inhibition accelerates directed hCM differentiation from hESC, and that this effect is developmental stage-specific. The use of this inhibitor should improve our ability to generate hESC-derived hCM for cell-based therapy.
Enhanced cardiomyogenesis of human embryonic stem cells by a small molecular inhibitor of p38 MAPK. Differentiation 2008 APR
Abstract
Human embryonic stem cells (hESC) can differentiate to cardiomyocytes in vitro but with generally poor efficiency. Here, we describe a novel method for the efficient generation of cardiomyocytes from hESC in a scalable suspension culture process. Differentiation in serum-free medium conditioned by the cell line END2 (END2-CM) readily resulted in differentiated cell populations with more than 10% cardiomyocytes without further enrichment. By screening candidate molecules, we have identified SB203580, a specific p38 MAP kinase inhibitor, as a potent promoter of hESC-cardiogenesis. SB203580 at concentrations textless10 microM, induced more than 20% of differentiated cells to become cardiomyocytes and increased total cell numbers, so that the overall cardiomyocyte yield was approximately 2.5-fold higher than controls. Gene expression indicated that early mesoderm formation was favored in the presence of SB203580. Accordingly, transient addition of the inhibitor at the onset of differentiation only was sufficient to determine the hESC fate. Patch clamp electrophysiology showed that the distribution of cardiomyocyte phenotypes in the population was unchanged by the compound. Interestingly, cardiomyogenesis was strongly inhibited at SB203580 concentrations textgreater or =15 microM. Thus, modulation of the p38MAP kinase pathway, in combination with factors released by END2 cells, plays an essential role in early lineage determination in hESC and the efficiency of cardiomyogenesis. Our findings contribute to transforming human cardiomyocyte generation from hESC into a robust and scalable process.
更多信息
| Molecular Weight | 413.9 g/mol |
|---|---|
| 种属 | Human, Mouse, Non-Human Primate, Other, Rat |
| Alternative Names | PB 203580, RWJ 64809 |
| Cas Number | 869185-85-3 |
| Chemical Formula | C₂₁H₁₆FN₃OS · HCl |
| 纯度 | ≥ 95% |
| Target | p38 MAPK |
| Pathway | p38 MAPK |
质量保证:
产品仅供研究使用，不用于针对人或动物的诊断或治疗。
产品仅供研究使用，不用于针对人或动物的诊断或治疗。
