MUC1* Ligand, NM23-H1, is a Novel Growth Factor That Maintains Human Stem Cells in a More Naïve State

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Mar 19

PMID 23505541

Citations 13

Authors

Benoit J Smagghe

Andrew K Stewart

Mark G Carter

Laura M Shelton

Kyle J Bernier

Eric J Hartman

Amy K Calhoun

Vasilios M Hatziioannou

Gabriele Lillacci

Brian A Kirk

Brian A DiNardo

Kenneth S Kosik

Cynthia Bamdad

Affiliations

Soon will be listed here.

Abstract

We report that a single growth factor, NM23-H1, enables serial passaging of both human ES and iPS cells in the absence of feeder cells, their conditioned media or bFGF in a fully defined xeno-free media on a novel defined, xeno-free surface. Stem cells cultured in this system show a gene expression pattern indicative of a more "naïve" state than stem cells grown in bFGF-based media. NM23-H1 and MUC1* growth factor receptor cooperate to control stem cell self-replication. By manipulating the multimerization state of NM23-H1, we override the stem cell's inherent programming that turns off pluripotency and trick the cells into continuously replicating as pluripotent stem cells. Dimeric NM23-H1 binds to and dimerizes the extra cellular domain of the MUC1* transmembrane receptor which stimulates growth and promotes pluripotency. Inhibition of the NM23-H1/MUC1* interaction accelerates differentiation and causes a spike in miR-145 expression which signals a cell's exit from pluripotency.

Citing Articles

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