A fluorescent screening platform for the rapid evaluation of chemicals in cellular reprogramming

Marc Vendrell, Sung-Jin Park, Yogeswari Chandran, Chi-Lik Ken Lee, Hyung-Ho Ha, Nam-Young Kang, Seong-Wook Yun, Young-Tae Chang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Current strategies to monitor reprogramming into induced pluripotent stem cells (iPSCs) are limited in that they rely on the recognition of advanced stage biomarkers or they involve the transduction of genetically-modified cells. These limitations are particularly problematic in high-throughput screenings where cell availability, low cost and a rapid experimental protocol are critical issues. Herein we report the application of a pluripotent stem cell fluorescent probe (i.e. CDy1) as a reporter for the rapid screening of chemicals in reprogramming iPSCs. CDy1 stains early-stage iPSCs at 7 dpi as well as matured iPSCs; hence it can partially overcome the slow kinetics of the reprogramming process. As a proof of concept, we employed a CDy1-based screening in 384 well-plates to examine the effect of newly synthesized hydroxamic acid derivatives in reprogramming mouse fibroblasts transduced with Oct4, Sox2 and Klf-4 without c-Myc. One compound (1-26) was identified as a reprogramming enhancer by 2.5-fold and we confirmed that 1-26 behaves as a histone deacetylase (HDAC) inhibitor. The successful identification of novel small molecules enhancing the generation of iPSCs by means of a rapid and simple protocol demonstrates the suitability of this CDy1-based screening platform for the large scale and high-throughput evaluation of iPSC modulators. (C) 2012 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)185-191
Number of pages7
JournalStem Cell Research
Volume9
Issue number3
DOIs
Publication statusPublished - Nov 2012

Keywords

  • PLURIPOTENT STEM-CELLS
  • SMALL-MOLECULE COMPOUNDS
  • DRUG DISCOVERY
  • SOMATIC-CELLS
  • SELF-RENEWAL
  • FIBROBLASTS
  • GENERATION
  • INDUCTION
  • DIFFERENTIATION
  • PROMOTE

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