Low Cell-Matrix Adhesion Reveals Two Subtypes of Human Pluripotent Stem Cells

Stem Cell Reports. 2018 Jul 10;11(1):142-156. doi: 10.1016/j.stemcr.2018.06.003. Epub 2018 Jun 28.


We show that a human pluripotent stem cell (hPSC) population cultured on a low-adhesion substrate developed two hPSC subtypes with different colony morphologies: flat and domed. Notably, the dome-like cells showed higher active proliferation capacity and increased several pluripotent genes' expression compared with the flat monolayer cells. We further demonstrated that cell-matrix adhesion mediates the interaction between cell morphology and expression of KLF4 and KLF5 through a serum response factor (SRF)-based regulatory double loop. Our results provide a mechanistic view on the coupling among adhesion, stem cell morphology, and pluripotency, shedding light on the critical role of cell-matrix adhesion in the induction and maintenance of hPSC.

Keywords: cell-matrix adhesion; heterogeneity; human pluripotent stem cells; mathematical model; nanofiber; serum response factor; single-cell culture; stem cell morphology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Cell Adhesion / genetics
  • Cell Differentiation
  • Cell Proliferation
  • Cell Self Renewal / genetics
  • Cell-Matrix Junctions / metabolism*
  • Gene Expression
  • Humans
  • Immunophenotyping
  • Karyotype
  • Models, Biological
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism*


  • Biomarkers