In Silico Discovery of Small Molecules for Efficient Stem Cell Differentiation into Definitive Endoderm

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2023 Feb 21

PMID 36801003

Authors

Gherman Novakovsky

Shugo Sasaki

Oriol Fornes

Meltem E Omur

Helen Huang

Carmen L Bayly

Dahai Zhang

Nathaniel Lim

Artem Cherkasov

Paul Pavlidis

Sara Mostafavi

Francis C Lynn

Wyeth W Wasserman

Affiliations

Soon will be listed here.

Abstract

Improving methods for human embryonic stem cell differentiation represents a challenge in modern regenerative medicine research. Using drug repurposing approaches, we discover small molecules that regulate the formation of definitive endoderm. Among them are inhibitors of known processes involved in endoderm differentiation (mTOR, PI3K, and JNK pathways) and a new compound, with an unknown mechanism of action, capable of inducing endoderm formation in the absence of growth factors in the media. Optimization of the classical protocol by inclusion of this compound achieves the same differentiation efficiency with a 90% cost reduction. The presented in silico procedure for candidate molecule selection has broad potential for improving stem cell differentiation protocols.

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