A versatile polypharmacology platform promotes cytoprotection and viability of human pluripotent and differentiated cells

Yu Chen, Carlos A. Tristan, Lu Chen, Vukasin M. Jovanovic, Claire Malley, Pei Hsuan Chu, Seungmi Ryu, Tao Deng, Pinar Ormanoglu, Dingyin Tao, Yuhong Fang, Jaroslav Slamecka, Hyenjong Hong, Christopher A. LeClair, Sam Michael, Christopher P. Austin, Anton Simeonov, Ilyas Singeç

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Human pluripotent stem cells (hPSCs) are capable of extensive self-renewal yet remain highly sensitive to environmental perturbations in vitro, posing challenges to their therapeutic use. There is an urgent need to advance strategies that ensure safe and robust long-term growth and functional differentiation of these cells. Here, we deployed high-throughput screening strategies to identify a small-molecule cocktail that improves viability of hPSCs and their differentiated progeny. The combination of chroman 1, emricasan, polyamines, and trans-ISRIB (CEPT) enhanced cell survival of genetically stable hPSCs by simultaneously blocking several stress mechanisms that otherwise compromise cell structure and function. CEPT provided strong improvements for several key applications in stem-cell research, including routine cell passaging, cryopreservation of pluripotent and differentiated cells, embryoid body (EB) and organoid formation, single-cell cloning, and genome editing. Thus, CEPT represents a unique poly-pharmacological strategy for comprehensive cytoprotection, providing a rationale for efficient and safe utilization of hPSCs.

Original languageEnglish
Pages (from-to)528-541
Number of pages14
JournalNature Methods
Volume18
Issue number5
DOIs
StatePublished - 1 May 2021
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'A versatile polypharmacology platform promotes cytoprotection and viability of human pluripotent and differentiated cells'. Together they form a unique fingerprint.

Cite this