Human parthenogenetic embryonic stem cell-derived neural stem cells express HLA-G and show unique resistance to NK cell-mediated killing

Please always quote using this URN: urn:nbn:de:bvb:20-opus-149170
  • 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 immunogenicityParent-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.show moreshow less

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Metadaten
Author: Jessica Schmitt, Sigrid Eckardt, Paul G Schlegel, Anna-Leena Sirén, Valentin S Bruttel, K John McLaughlin, Jörg Wischhusen, Albrecht M Müller
URN:urn:nbn:de:bvb:20-opus-149170
Document Type:Journal article
Faculties:Medizinische Fakultät / Kinderklinik und Poliklinik
Medizinische Fakultät / Institut für Medizinische Strahlenkunde und Zellforschung
Language:English
Parent Title (English):Molecular Medicine
Year of Completion:2015
Volume:21
Issue:2101185
Pagenumber:185-196
Source:Molecular Medicine 21:2101185, 185-196 (2015). DOI: 10.2119/molmed.2014.00188
DOI:https://doi.org/10.2119/molmed.2014.00188
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:HLA-G gene; T lymphocytes; blastocysts; brain development; immune response; in vitro; lines; mhc molecules; nervous system; stem/progenitor cells
Release Date:2018/11/27
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International