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Inhibition of mitogen-activated protein kinase kinase, DNA methyltransferase, and transforming growth factor-β promotes differentiation of human induced pluripotent stem cells into enterocytes


, : Inhibition of mitogen-activated protein kinase kinase, DNA methyltransferase, and transforming growth factor-β promotes differentiation of human induced pluripotent stem cells into enterocytes. Drug Metabolism and Pharmacokinetics 31(3): 193-200

We previously reported that small-molecule compounds were effective in generating pharmacokinetically functional enterocytes from human induced pluripotent stem (iPS) cells. In this study, to determine whether the compounds promote the differentiation of human iPS cells into enterocytes, we investigated the effects of a combination of mitogen-activated protein kinase kinase (MEK), DNA methyltransferase (DNMT), and transforming growth factor (TGF)-β inhibitors on intestinal differentiation. Human iPS cells cultured on feeder cells were differentiated into endodermal cells by activin A. These endodermal-like cells were then differentiated into intestinal stem cells by fibroblast growth factor 2. Finally, the cells were differentiated into enterocyte cells by epidermal growth factor and small-molecule compounds. After differentiation, mRNA expression levels and drug-metabolizing enzyme activities were measured. The mRNA expression levels of the enterocyte marker sucrase-isomaltase and the major drug-metabolizing enzyme cytochrome P450 (CYP) 3A4 were increased by a combination of MEK, DNMT, and TGF-β inhibitors. The mRNA expression of CYP3A4 was markedly induced by 1α,25-dihydroxyvitamin D3. Metabolic activities of CYP1A1/2, CYP2B6, CYP2C9, CYP2C19, CYP3A4/5, UDP-glucuronosyltransferase, and sulfotransferase were also observed in the differentiated cells. In conclusion, MEK, DNMT, and TGF-β inhibitors can be used to promote the differentiation of human iPS cells into pharmacokinetically functional enterocytes.

US$19.90

PMID: 27161454

DOI: 10.1016/j.dmpk.2016.02.002


Other references

Spinelli, F.; Massara, M.; L.S.ada, M.; Stilo, F.; Barillà, D.; D.C.ridi, G., 2014: A simple technique to achieve bloodless excision of carotid body tumors. We describe a technique for Shamblin II-III carotid body tumor (CBT) resection to reduce bleeding and neurologic complications during surgery. The technique was based on the fact that CBTs are supplied almost exclusively from the external carotid...

Stroshine, R.L.; Cooke, J.R.; Rand, R.H.; Cutler, J.M.; Chabot, J.F., 1979: Mathematical analysis of pressure chamber efflux curves. The pressure chamber is widely used to measure plant water potential. This mathematical and experimental study relates anatomical features of wheat leaves to the rate at which water can be forced from them in the chamber. Only the small veins offe...

Ishizawa M., 1985: Mechanical actions of prostaglandins on the sartorius muscle of frog. Journal of the Physiological Society of Japan 47(8-9): 518

Samoto, M.M.ebuchi, M.M.yazaki, C.K.gitani, H.K.hno, M.H.rotsuka, M.K.to, M., 2007: Abundant proteins associated with lecithin in soy protein isolate. A new method for fractionating acid-precipitated soy proteins, so called soy protein isolate, involving three step acidification of a water extract of defatted soy flour was developed. Soy protein isolate was shown to be mostly composed of not onl...

Todaro-Franceschi, V., 2009: Using an online community board for end-of-life care teaching, learning, and student engagement. Nurse Educator 34(4): 150-151

Wood, P.J.; Fulcher, R.G., 1983: Dye interactions. A basis for specific detection and histochemistry of polysaccharides. Specific histochemical staining can be related to specific interactions of dyes and polysaccharides in solution. Specificity evidently depends upon polysaccharide conformation and the need for a close "fit" between polysaccharide and lig...

Politiek, R.D., 1965: Milkability and milk yield of heifers. The relationship between maximum milk flow rate and average daily milk yield in the 1st lactation was studied in 26 daughter groups (644 heifers) in Overijssel and 15 daughter groups (368 heifers) in North Holland. Within daughter groups the corre...

Worling, J.R., 2001: Personality-based typology of adolescent male sexual offenders: differences in recidivism rates, victim-selection characteristics, and personal victimization histories. California Psychological Inventory scores from 112 adolescent male sexual offenders aged 12-19 (M = 15.59, SD = 1.46) were examined. A cluster analysis of factor-derived scores revealed four personality-based subgroups: Antisocial/Impulsive, Unusu...

Deheeger, M.; Rolland-Cachera, M.F.; Péquignot, F.; Labadie, M.D.; Rossignol, C., 1988: Feeding of 10-month-old infants. What problems? What solutions?. The feeding of 279 infants aged 10 months was evaluated by the dietary history method, in Paris health centers for children. The results of this survey, as compared with the recommended dietary allowances of the Centre National de Coordination des...

Hampacherová, M.; Koutecká, E.; Neubauer, Z., 1973: Two repressors in bacteriophage lambda. Molecular & General Genetics 120(2): 133-137