MUC1* ligand, NM23-H1, is a novel growth factor that maintains human stem cells in a more naïve state

PLoS One. 2013;8(3):e58601. doi: 10.1371/journal.pone.0058601. Epub 2013 Mar 7.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • Binding, Competitive
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / metabolism
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblasts / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / metabolism
  • Ligands
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Mucin-1 / immunology
  • Mucin-1 / metabolism
  • NM23 Nucleoside Diphosphate Kinases / chemistry
  • NM23 Nucleoside Diphosphate Kinases / metabolism
  • NM23 Nucleoside Diphosphate Kinases / pharmacology*
  • Protein Binding / drug effects
  • Protein Multimerization
  • Stem Cells / cytology
  • Stem Cells / drug effects*
  • Stem Cells / metabolism

Substances

  • Antibodies, Monoclonal
  • Biomarkers
  • Culture Media, Conditioned
  • Ligands
  • MIRN145 microRNA, human
  • MicroRNAs
  • Mucin-1
  • NM23 Nucleoside Diphosphate Kinases
  • Fibroblast Growth Factor 2

Grants and funding

The work of GL was supported by the National Science Foundation under Grant NSF-CDI ECC-0835847. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.