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Stem Cells International - Volume 2016 2016, Article ID 2574152, 11 pages -

Research Article

Section of Hematology and Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA

Center for Regenerative Medicine CReM, Boston University and Boston Medical Center, Boston, MA 02118, USA

Department of Environmental Health, Boston University School of Public Health, Boston, MA 02118, USA

Received 4 January 2016; Accepted 17 March 2016

Academic Editor: Fanny L. Casado

Copyright © 2016 Brenden W. Smith et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The aryl hydrocarbon receptor AHR is a ligand activated transcription factor that increases the expression of detoxifying enzymes upon ligand stimulation. Recent studies now suggest that novel endogenous roles of the AHR exist throughout development. In an effort to create an optimized model system for the study of AHR signaling in several cellular lineages, we have employed a CRISPR-CAS9 genome editing strategy in induced pluripotent stem cells iPSCs to incorporate a reporter cassette at the transcription start site of one of its canonical targets, cytochrome P450 1A1 CYP1A1. This cell line faithfully reports on CYP1A1 expression, with luciferase levels as its functional readout, when treated with an endogenous AHR ligand FICZ at escalating doses. iPSC-derived fibroblast-like cells respond to acute exposure to environmental and endogenous AHR ligands, and iPSC-derived hepatocytes increase CYP1A1 in a similar manner to primary hepatocytes. This cell line is an important innovation that can be used to map AHR activity in discrete cellular subsets throughout developmental ontogeny. As further endogenous ligands are proposed, this line can be used to screen for safety and efficacy and can report on the ability of small molecules to regulate critical cellular processes by modulating the activity of the AHR.





Autor: Brenden W. Smith, Elizabeth A. Stanford, David H. Sherr, and George J. Murphy

Fuente: https://www.hindawi.com/



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