Document Type

Article

Publication Date

2-8-2022

Publication Title

Stem Cell Reports

Keywords

JMG, Animals, Apoptosis, Autophagy, Cell Line, Cell Survival, DNA, Embryonic Stem Cells, Enzyme Inhibitors, Female, G1 Phase, Humans, Hydrazines, Mice, Mice, Nude, Phosphatidylinositol 3-Kinases, Pluripotent Stem Cells, Teratocarcinoma, Transplantation, Heterologous

JAX Source

Stem Cell Reports 2022 Feb 8; 17:397-412

Volume

17

Issue

2

First Page

397

Last Page

412

ISSN

2213-6711

PMID

35063131

DOI

https://doi.org/10.1016/j.stemcr.2021.12.013

Abstract

Inhibition of PIKfyve phosphoinositide kinase selectively kills autophagy-dependent cancer cells by disrupting lysosome homeostasis. Here, we show that PIKfyve inhibitors can also selectively eliminate pluripotent embryonal carcinoma cells (ECCs), embryonic stem cells, and induced pluripotent stem cells under conditions where differentiated cells remain viable. PIKfyve inhibitors prevented lysosome fission, induced autophagosome accumulation, and reduced cell proliferation in both pluripotent and differentiated cells, but they induced death only in pluripotent cells. The ability of PIKfyve inhibitors to distinguish between pluripotent and differentiated cells was confirmed with xenografts derived from ECCs. Pretreatment of ECCs with the PIKfyve specific inhibitor WX8 suppressed their ability to form teratocarcinomas in mice, and intraperitoneal injections of WX8 into mice harboring teratocarcinoma xenografts selectively eliminated pluripotent cells. Differentiated cells continued to proliferate, but at a reduced rate. These results provide a proof of principle that PIKfyve specific inhibitors can selectively eliminate pluripotent stem cells in vivo as well as in vitro.

Comments

This is an open access article under the CC BY-NC-ND IGO license.

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