RepSox is a cell permeable, selective inhibitor of the TGF-β type 1 receptor (TGFβRI) ALK5 (IC₅₀ = 4, 18, and 23 nM for ALK5 autophosphorylation, TGF-β cellular assay, and ALK5 binding in HepG2 cells, respectively; Gellibert et al.). This inhibitor demonstrated less potent activity (IC₅₀ > 16 μM) against 9 related kinases, including p38 MAPK and GSK3 (Gellibert et al.). This product is supplied as the hydrochloride salt of the molecule.
REPROGRAMMING
· Enhances reprogramming of mouse embryonic fibroblasts (MEFs) that have been transduced with OCT4, KLF4, and c-MYC (Ichida et al.; Subramanyam et al.)
· Direct lineage reprogramming of fibroblasts to mature neurons, in combination with CHIR99021, Valproic Acid, Forskolin, SP600125, Gö6983 and Y-27632 (Hu et al.).
DIFFERENTIATION
· Alone or in combination with forskolin, dexamethasone, and nicotinamide, induces differentiation of human pancreatic progenitor cells into insulin-producing cells (Kunisada et al.; Rezania et al.).
REPROGRAMMING
· Enhances reprogramming of mouse embryonic fibroblasts (MEFs) that have been transduced with OCT4, KLF4, and c-MYC (Ichida et al.; Subramanyam et al.)
· Direct lineage reprogramming of fibroblasts to mature neurons, in combination with CHIR99021, Valproic Acid, Forskolin, SP600125, Gö6983 and Y-27632 (Hu et al.).
DIFFERENTIATION
· Alone or in combination with forskolin, dexamethasone, and nicotinamide, induces differentiation of human pancreatic progenitor cells into insulin-producing cells (Kunisada et al.; Rezania et al.).
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Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Applications
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Resources and Publications
Educational Materials (3)
Publications (6)
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 molecules induce efficient differentiation into insulin-producing cells from human induced pluripotent stem cells. Stem cell research 2012 MAR
Abstract
Human induced pluripotent stem (hiPS) cells have potential uses for drug discovery and cell therapy, including generation of pancreatic β-cells for diabetes research and treatment. In this study, we developed a simple protocol for generating insulin-producing cells from hiPS cells. Treatment with activin A and a GSK3β inhibitor enhanced efficient endodermal differentiation, and then combined treatment with retinoic acid, a bone morphogenic protein inhibitor, and a transforming growth factor-β (TGF-β) inhibitor induced efficient differentiation of pancreatic progenitor cells from definitive endoderm. Expression of the pancreatic progenitor markers PDX1 and NGN3 was significantly increased at this step and most cells were positive for anti-PDX1 antibody. Moreover, several compounds, including forskolin, dexamethasone, and a TGF-β inhibitor, were found to induce the differentiation of insulin-producing cells from pancreatic progenitor cells. By combined treatment with these compounds, more than 10% of the cells became insulin positive. The differentiated cells secreted human c-peptide in response to various insulin secretagogues. In addition, all five hiPS cell lines that we examined showed efficient differentiation into insulin-producing cells with this protocol.
Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells. Nature biotechnology 2011 MAY
Abstract
The embryonic stem cell-specific cell cycle-regulating (ESCC) family of microRNAs (miRNAs) enhances reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells. Here we show that the human ESCC miRNA orthologs hsa-miR-302b and hsa-miR-372 promote human somatic cell reprogramming. Furthermore, these miRNAs repress multiple target genes, with downregulation of individual targets only partially recapitulating the total miRNA effects. These targets regulate various cellular processes, including cell cycle, epithelial-mesenchymal transition (EMT), epigenetic regulation and vesicular transport. ESCC miRNAs have a known role in regulating the unique embryonic stem cell cycle. We show that they also increase the kinetics of mesenchymal-epithelial transition during reprogramming and block TGFβ-induced EMT of human epithelial cells. These results demonstrate that the ESCC miRNAs promote dedifferentiation by acting on multiple downstream pathways. We propose that individual miRNAs generally act through numerous pathways that synergize to regulate and enforce cell fate decisions.
PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED. FOR ADDITIONAL INFORMATION ON QUALITY AT STEMCELL, REFER TO WWW.STEMCELL.COM/COMPLIANCE.
