产品号 #72112_C
cAMP 通路激活剂；激活腺苷酸环化酶
总览
Forskolin是一种可穿透细胞的二萜，可直接激活腺苷酸环化酶 (IC₅₀ = 41 nM)，该酶可产生环磷酸腺苷 (cAMP)，从而提高细胞内的 cAMP 水平。cAMP 是参与许多信号转导途径的重要第二信使，包括激活蛋白激酶 A (PKA; Awad et al.; Robbins et al.)。
重编程
·与 CHIR99021、Tranylcypromine、 Valproic Acid、3-Deazaneplanocin A 和 RepSox 结合，使小鼠胚胎成纤维细胞能够化学重编程（无遗传因素）为诱导多能干 (iPS) 细胞。（Hou et al.）。
·使 NGN2 介导的人成纤维细胞向胆碱能神经元的转分化（Liu et al.）。
·与 RepSox、CHIR99021、SP600125、丙戊酸、Gö6983 和 Y-27632 联合使用，可将成纤维细胞直接谱系重编程为成熟神经元（Hu et al）。
·与 CHIR99021、ISX-9、SB431542 和 I-BET151 联合使用，可将成纤维细胞直接谱系重编程为成熟神经元（Li et al.）。
·与 LIF、FGF2、TGFβ 和小分子 PD0325901、CHIR99021、SP600125 和 SB203580 联合使用，可将处于“naïve”状态或 ground state 的人胚胎干细胞 (ES) 转化为类似于小鼠 ES 细胞的细胞（Hanna et al.）。
分化
·增强大鼠海马神经祖细胞的神经元分化（Hsieh et al., Palmer et al.）。
细胞类型
神经干/祖细胞，神经元，多能干细胞
种属
人，小鼠，非人灵长类，其它细胞系，大鼠
应用
培养，重编程
研究领域
神经科学，干细胞生物学
CAS 编号
66575-29-9
化学式
C₂₂H₃₄O₇
纯度
≥98%
通路
cAMP
靶点
腺苷酸环化酶
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Applications
This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.
Resources and Publications
Educational Materials (4)
Publications (9)
Direct Conversion of Normal and Alzheimer's Disease Human Fibroblasts into Neuronal Cells by Small Molecules. Cell stem cell 2015 AUG
Abstract
Neuronal conversion from human fibroblasts can be induced by lineage-specific transcription factors; however, the introduction of ectopic genes limits the therapeutic applications of such induced neurons (iNs). Here, we report that human fibroblasts can be directly converted into neuronal cells by a chemical cocktail of seven small molecules, bypassing a neural progenitor stage. These human chemical-induced neuronal cells (hciNs) resembled hiPSC-derived neurons and human iNs (hiNs) with respect to morphology, gene expression profiles, and electrophysiological properties. This approach was further applied to generate hciNs from familial Alzheimer's disease patients. Taken together, our transgene-free and chemical-only approach for direct reprogramming of human fibroblasts into neurons provides an alternative strategy for modeling neurological diseases and for regenerative medicine.
Small-Molecule-Driven Direct Reprogramming of Mouse Fibroblasts into Functional Neurons. Cell stem cell 2015 AUG
Abstract
Recently, direct reprogramming between divergent lineages has been achieved by the introduction of regulatory transcription factors. This approach may provide alternative cell resources for drug discovery and regenerative medicine, but applications could be limited by the genetic manipulation involved. Here, we show that mouse fibroblasts can be directly converted into neuronal cells using only a cocktail of small molecules, with a yield of up to textgreater90% being TUJ1-positive after 16 days of induction. After a further maturation stage, these chemically induced neurons (CiNs) possessed neuron-specific expression patterns, generated action potentials, and formed functional synapses. Mechanistically, we found that a BET family bromodomain inhibitor, I-BET151, disrupted the fibroblast-specific program, while the neurogenesis inducer ISX9 was necessary to activate neuron-specific genes. Overall, our findings provide a proof of principle" for chemically induced direct reprogramming of somatic cell fates across germ layers without genetic manipulation�
Small molecules enable neurogenin 2 to efficiently convert human fibroblasts into cholinergic neurons. Nature communications 2013 JAN
Abstract
Cell fate can be reprogrammed by modifying intrinsic and extrinsic cues. Here we show that two small molecules (forskolin and dorsomorphin) enable the transcription factor Neurogenin 2 (NGN2) to convert human fetal lung fibroblasts into cholinergic neurons with high purity (textgreater90%) and efficiency (up to 99% of NGN2-expressing cells). The conversion is direct without passing through a proliferative progenitor state. These human induced cholinergic neurons (hiCN) show mature electrophysiological properties and exhibit motor neuron-like features, including morphology, gene expression and the formation of functional neuromuscular junctions. Inclusion of an additional transcription factor, SOX11, also efficiently converts postnatal and adult skin fibroblasts from healthy and diseased human patients to cholinergic neurons. Taken together, this study identifies a simple and highly efficient strategy for reprogramming human fibroblasts to subtype-specific neurons. These findings offer a unique venue for investigating the molecular mechanisms underlying cellular plasticity and human neurodegenerative diseases.
更多信息
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 66575-29-9 |
| Chemical Formula | C₂₂H₃₄O₇ |
| Purity | ≥ 98% |
| Target | Adenylyl Cyclase |
| Pathway | cAMP |
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