Evidence map›Paper›PMID 35063131›Full record

ArticleStem cell reports2022

Selective elimination of pluripotent stem cells by PIKfyve specific inhibitors.

Arup R Chakraborty, Alex Vassilev, Sushil K Jaiswal, Constandina E O'Connell, John F Ahrens, Barbara S Mallon, Martin F Pera, Melvin L DePamphilis

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.4field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Review
  3. PIKfyve mediates the maturation of mycobacteria-containing vesicles.Frontiers in cellular and infection microbiology · 2026
    Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Strategies to Improve the Safety of iPSC-Derived β Cells for β Cell Replacement in Diabetes.Transplant international : official journal of the European Society for Organ Transplantation · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 1 country.

Arup R ChakrabortyNational Institute of Child Health & Human Development, National Institutes of Health, Bldg. 6A/3A15, 6 Center Drive, Bethesda, MD 20892-2790, USA.
Alex VassilevNational Institute of Child Health & Human Development, National Institutes of Health, Bldg. 6A/3A15, 6 Center Drive, Bethesda, MD 20892-2790, USA.
Sushil K JaiswalNational Institute of Child Health & Human Development, National Institutes of Health, Bldg. 6A/3A15, 6 Center Drive, Bethesda, MD 20892-2790, USA.
Constandina E O'ConnellNational Institute of Child Health & Human Development, National Institutes of Health, Bldg. 6A/3A15, 6 Center Drive, Bethesda, MD 20892-2790, USA.
John F AhrensNational Institute of Child Health & Human Development, National Institutes of Health, Bldg. 6A/3A15, 6 Center Drive, Bethesda, MD 20892-2790, USA.
Barbara S MallonNIH Stem Cell Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Martin F PeraThe Jackson Laboratory, Bar Harbor, ME, USA.
Melvin L DePamphilisNational Institute of Child Health & Human Development, National Institutes of Health, Bldg. 6A/3A15, 6 Center Drive, Bethesda, MD 20892-2790, USA. Electronic address: depamphm@mail.nih.gov.
Eunice Kennedy Shriver National Institute of Child Health and Human Development · USNational Institutes of Health · USJackson Laboratory · USNational Institute of Neurological Disorders and Stroke · US

Funding

Initiation Of DNA Replication In Mammalian ChromosomesZIAHD000506 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI DEPAMPHILIS, MELVIN · 2009 to 2023
$15.4M
Gene Expression At The Beginning Of Mammalian DevelopmentZIAHD000507 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI DEPAMPHILIS, MELVIN · 2009 to 2018
$8.6M
Intramural NIH HHS ZIA HD000506Intramural NIH HHS ZIA HD000507
6 · The paper itself

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.

Indexed as

AnimalsApoptosisAutophagyCell LineCell SurvivalDNAEmbryonic Stem CellsEnzyme InhibitorsFemaleG1 PhaseHumansHydrazinesMiceMice, NudePhosphatidylinositol 3-KinasesPluripotent Stem CellsDNAEnzyme InhibitorshydrazineHydrazinesPhosphatidylinositol 3-KinasesPIKFYVE protein, humanautophagosomeautophagycancer stem cellsembryonal carcinoma stem cellsembryonic stem cellsinduced pluripotent stem cellslysosome

Identifiers

PMID35063131
PMCPMC8828683
OpenAlexW4206648458

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.