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- 학술저널
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- 2017.1
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Human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), represent potentially unlimited cell sources for clinical applications. Previous studies have suggested that hPSCs may benefit from immune privilege and limited immunogenicity, as reflected by the reduced expression of major histocompatibility complex class-related molecules.
Here we investigated the global immune-related gene expression profiles of human ESCs, hiPSCs and somatic cells and identified candidate immune-related genes that may alter their immunogenicity. The expression levels of global immune-related genes were determined by comparing undifferentiated and differentiated stem cells and three types of human somatic cells: dermal papilla cells, ovarian granulosa cells and foreskin fibroblast cells. We identified the differentially expressed genes CD24, GATA3, PROM1, THBS2, LY96, IFIT3, CXCR4, IL1R1, FGFR3, IDO1 and KDR, which overlapped with selected immune-related gene lists. In further analyses, mammalian target of rapamycin complex (mTOR) signaling was investigated in the differentiated stem cells following treatment with rapamycin and lentiviral transduction with specific short-hairpin RNAs. We found that the inhibition of mTOR signal pathways significantly downregulated the immunogenicity of differentiated stem cells. We also tested the immune responses induced in differentiated stem cells by mixed lymphocyte reactions. We found that CD24- and GATA3-deficient differentiated stem cells including neural lineage cells had limited abilities to activate human lymphocytes. By analyzing the transcriptome signature of immune-related genes, we observed a tendency of the hPSCs to differentiate toward an immune cell phenotype. Taken together, these data identify candidate immune-related genes that might constitute valuable targets for clinical applications.
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참고문헌 (24)
참고문헌 신청
Araki R / 2013 / Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells / Nature 494 : 100 ~ 104
Bonde S / 2006 / Immunogenicity and engraftment of mouse embryonic stem cells in allogeneic recipients / Stem Cells 24 : 2192 ~ 2201
Bonde S / 2008 / ES-cell derived hematopoietic cells induce transplantation tolerance / PLoS ONE 3 : e3212 ~
Burridge PW / 2011 / A universal system for highly efficient cardiac differentiation of human induced pluripotent stem cells that eliminates interline variability / PLoS ONE
Chen HF / 2007 / Derivation, characterization and differentiation of human embryonic stem cells: comparing serum-containing versus serum-free media and evidence of germ cell
Bonde S / 2006 / Immunogenicity and engraftment of mouse embryonic stem cells in allogeneic recipients / Stem Cells 24 : 2192 ~ 2201
Bonde S / 2008 / ES-cell derived hematopoietic cells induce transplantation tolerance / PLoS ONE 3 : e3212 ~
Burridge PW / 2011 / A universal system for highly efficient cardiac differentiation of human induced pluripotent stem cells that eliminates interline variability / PLoS ONE
Chen HF / 2007 / Derivation, characterization and differentiation of human embryonic stem cells: comparing serum-containing versus serum-free media and evidence of germ cell
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