Small Molecules Facilitate Rapid and Synchronous IPSC Generation

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2014 Sep 29

PMID 25262205

Citations 51

Authors

Ori Bar-Nur

Justin Brumbaugh

Cassandra Verheul

Effie Apostolou

Iulian Pruteanu-Malinici

Ryan M Walsh

Sridhar Ramaswamy

Konrad Hochedlinger

Affiliations

Soon will be listed here.

Abstract

The reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) upon overexpression of OCT4, KLF4, SOX2 and c-MYC (OKSM) provides a powerful system to interrogate basic mechanisms of cell fate change. However, iPSC formation with standard methods is typically protracted and inefficient, resulting in heterogeneous cell populations. We show that exposure of OKSM-expressing cells to both ascorbic acid and a GSK3-β inhibitor (AGi) facilitates more synchronous and rapid iPSC formation from several mouse cell types. AGi treatment restored the ability of refractory cell populations to yield iPSC colonies, and it attenuated the activation of developmental regulators commonly observed during the reprogramming process. Moreover, AGi supplementation gave rise to chimera-competent iPSCs after as little as 48 h of OKSM expression. Our results offer a simple modification to the reprogramming protocol, facilitating iPSC induction at unparalleled efficiencies and enabling dissection of the underlying mechanisms in more homogeneous cell populations.

Citing Articles

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