HLA-G expression in human embryonic stem cells and preimplantation embryos.
Human leukocyte Ag-G, a tolerogenic molecule that acts on cells of both innate and adaptive immunity, plays an important role in tumor progression, transplantation, placentation, as well as the protection of the allogeneic fetus from the maternal immune system. We investigated HLA-G mRNA and protein expression in human embryonic stem cells (hESC) derived from the inner cell mass (ICM) of blastocysts. hESC self-renew indefinitely in culture while maintaining pluripotency, providing an unlimited source of cells for therapy. HLA-G mRNA was present in early and late passage hESC, as assessed by real time RT-PCR. Protein expression was demonstrated by flow cytometry, immunocytochemistry, and ELISA on an hESC extract. Binding of HLA-G with its ILT2 receptor demonstrated the functional active status. To verify this finding in a physiologically relevant setting, HLA-G protein expression was investigated during preimplantation development. We demonstrated HLA-G protein expression in oocytes, cleavage stage embryos, and blastocysts, where we find it in trophectoderms but also in ICM cells. During blastocyst development, a downregulation of HLA-G in the ICM cells was present. This data might be important for cell therapy and transplantation because undifferentiated hESC can contaminate the transplant of differentiated stem cells and develop into malignant cancer cells.
Department of Hematology, University Hospital Brussels, 1090 Brussels, Belgium.
An
A
Verloes
Hilde
H
Van de Velde
Joel
J
LeMaoult
Ileana
I
Mateizel
Greet
G
Cauffman
Peter A
PA
Horn
Edgardo D
ED
Carosella
Paul
P
Devroey
Marc
M
De Waele
Vera
V
Rebmann
Martine
M
Vercammen
D015703:Antigens, CD / Q000378:metabolism; D053624:Blastocyst Inner Cell Mass / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002970:Cleavage Stage, Ovum / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000276:immunology* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D009865:Oocytes / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism
D015703:Antigens, CD; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D020033:Protein Isoforms; D011971:Receptors, Immunologic