SP600125 is a potent and reversible inhibitor of JNK1-3 (IC₅₀ = 0.11 μM) (Bennett et al.). It is cell-permeable and dose-dependently inhibits c-JUN phosphorylation in cells, blocking the expression of COX-2 and TNF-α in monocytes and IL-10, TNF-α, and IFN- in T-cells (Bennett et al.).
REPROGRAMMING
· Direct lineage reprogramming of fibroblasts to mature neurons, in combination with CHIR99021, RepSox, Forskolin, Gö6983, Valproic Acid and Y-27632 (Hu et al.).
DIFFERENTIATION
· Inhibits BMP9-induced osteogenic differentiation in cultured mouse mesenchymal stem cells (MSCs) and in primary bone marrow stromal cells (Zhao et al.).
· Promotes adipogenic, but represses osteogenic differentiation of human MSCs (Bilkovski et al.; Liu et al.; Qiu et al.; Tominaga et al.).
· Causes cell death and inhibits neurogenesis when added during early stages of neuronal culture (Tiwari et al.).
REPROGRAMMING
· Direct lineage reprogramming of fibroblasts to mature neurons, in combination with CHIR99021, RepSox, Forskolin, Gö6983, Valproic Acid and Y-27632 (Hu et al.).
DIFFERENTIATION
· Inhibits BMP9-induced osteogenic differentiation in cultured mouse mesenchymal stem cells (MSCs) and in primary bone marrow stromal cells (Zhao et al.).
· Promotes adipogenic, but represses osteogenic differentiation of human MSCs (Bilkovski et al.; Liu et al.; Qiu et al.; Tominaga et al.).
· Causes cell death and inhibits neurogenesis when added during early stages of neuronal culture (Tiwari et al.).
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Protocols and Documentation
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Resources and Publications
Educational Materials (2)
Publications (8)
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.
Activation of JNKs is essential for BMP9-induced osteogenic differentiation of mesenchymal stem cells. BMB reports 2013 AUG
Abstract
Although BMP9 is highly capable of promoting osteogenic differentiation of mesenchymal stem cell (MSCs), the molecular mechanism involved remains to be fully elucidated. Here, we explore the possible involvement and detail role of JNKs (c-Jun N-terminal kinases) in BMP9-induced osteogenic differentiation of MSCs. It was found that BMP9 stimulated the activation of JNKs in MSCs. BMP9-induced osteogenic differentiation of MSCs was dramatically inhibited by JNKs inhibitor SP600125. Moreover, BMP9-activated Smads signaling was decreased by SP600125 treatment in MSCs. The effects of inhibitor are reproduced with adenoviruses expressing siRNA targeted JNKs. Taken together, our results revealed that JNKs was activated in BMP9-induced osteogenic differentiation of MSCs. What is most noteworthy, however, is that inhibition of JNKs activity resulted in reduction of BMP9-induced osteogenic differentiation of MSCs, implying that activation of JNKs is essential for BMP9 osteoinductive activity.
A chromatin-modifying function of JNK during stem cell differentiation. Nature genetics 2012 JAN
Abstract
Signaling mediates cellular responses to extracellular stimuli. The c-Jun NH(2)-terminal kinase (JNK) pathway exemplifies one subgroup of the mitogen-activated protein (MAP) kinases, which, besides having established functions in stress response, also contribute to development by an unknown mechanism. We show by genome-wide location analysis that JNK binds to a large set of active promoters during the differentiation of stem cells into neurons. JNK-bound promoters are enriched with binding motifs for the transcription factor NF-Y but not for AP-1. NF-Y occupies these predicted sites, and overexpression of dominant-negative NF-YA reduces the JNK presence on chromatin. We find that histone H3 Ser10 (H3S10) is a substrate for JNK, and JNK-bound promoters are enriched for H3S10 phosphorylation. Inhibition of JNK signaling in post-mitotic neurons reduces phosphorylation at H3S10 and the expression of target genes. These results establish MAP kinase binding and function on chromatin at a novel class of target genes during stem cell differentiation.
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