Human Parthenogenetic Embryonic Stem Cell-Derived Neural Stem Cells Express HLA-G and Show Unique Resistance to NK Cell-Mediated Killing

Mol Med. 2015 Mar 23;21(1):185-96. doi: 10.2119/molmed.2014.00188.


Parent-of-origin imprints have been implicated in the regulation of neural differentiation and brain development. Previously we have shown that, despite the lack of a paternal genome, human parthenogenetic (PG) embryonic stem cells (hESCs) can form proliferating neural stem cells (NSCs) that are capable of differentiation into physiologically functional neurons while maintaining allele-specific expression of imprinted genes. Since biparental ("normal") hESC-derived NSCs (N NSCs) are targeted by immune cells, we characterized the immunogenicity of PG NSCs. Flow cytometry and immunocytochemistry revealed that both N NSCs and PG NSCs exhibited surface expression of human leukocyte antigen (HLA) class I but not HLA-DR molecules. Functional analyses using an in vitro mixed lymphocyte reaction assay resulted in less proliferation of peripheral blood mononuclear cells (PBMC) with PG compared with N NSCs. In addition, natural killer (NK) cells cytolyzed PG less than N NSCs. At a molecular level, expression analyses of immune regulatory factors revealed higher HLA-G levels in PG compared with N NSCs. In line with this finding, MIR152, which represses HLA-G expression, is less transcribed in PG compared with N cells. Blockage of HLA-G receptors ILT2 and KIR2DL4 on natural killer cell leukemia (NKL) cells increased cytolysis of PG NSCs. Together this indicates that PG NSCs have unique immunological properties due to elevated HLA-G expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Apoptosis / immunology
  • Cell Differentiation*
  • Cell Line
  • Cytotoxicity, Immunologic*
  • Embryonic Stem Cells / cytology*
  • Gene Expression Regulation
  • Gene Expression*
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / immunology
  • HLA-DR Antigens / metabolism
  • HLA-G Antigens / genetics*
  • HLA-G Antigens / immunology
  • HLA-G Antigens / metabolism
  • Humans
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • MicroRNAs / genetics
  • Neural Stem Cells / cytology
  • Neural Stem Cells / immunology*
  • Neural Stem Cells / metabolism*


  • HLA-DR Antigens
  • HLA-G Antigens
  • MIRN152 microRNA, human
  • MicroRNAs