Comparative global immune-related gene profiling of somatic cells, human pluripotent stem cells and their derivatives: Implication for human lymphocyte proliferation

Chia Eng Wu, Chen Wei Yu, Kai Wei Chang, Wen Hsi Chou, Chen Yu Lu, Elisa Ghelfi, Fang Chun Wu, Pey Shynan Jan, Mei Chi Huang, Patrick Allard, Shau Ping Lin, Hong Nerng Ho, Hsin Fu Chen

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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. r The Author(s) 2017.

Original languageEnglish
Article numbere376
JournalExperimental and Molecular Medicine
Volume49
Issue number9
DOIs
Publication statusPublished - Sep 1 2017
Externally publishedYes

Fingerprint

Pluripotent Stem Cells
Lymphocytes
Stem cells
Genes
Derivatives
Sirolimus
Stem Cells
Transcriptome
Foreskin
Mixed Lymphocyte Culture Test
Neural Stem Cells
Granulosa Cells
Embryonic Stem Cells
Major Histocompatibility Complex
Small Interfering RNA
Signal Transduction
Down-Regulation
Fibroblasts
Gene expression
Phenotype

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Comparative global immune-related gene profiling of somatic cells, human pluripotent stem cells and their derivatives : Implication for human lymphocyte proliferation. / Wu, Chia Eng; Yu, Chen Wei; Chang, Kai Wei; Chou, Wen Hsi; Lu, Chen Yu; Ghelfi, Elisa; Wu, Fang Chun; Jan, Pey Shynan; Huang, Mei Chi; Allard, Patrick; Lin, Shau Ping; Ho, Hong Nerng; Chen, Hsin Fu.

In: Experimental and Molecular Medicine, Vol. 49, No. 9, e376, 01.09.2017.

Research output: Contribution to journalArticle

Wu, Chia Eng ; Yu, Chen Wei ; Chang, Kai Wei ; Chou, Wen Hsi ; Lu, Chen Yu ; Ghelfi, Elisa ; Wu, Fang Chun ; Jan, Pey Shynan ; Huang, Mei Chi ; Allard, Patrick ; Lin, Shau Ping ; Ho, Hong Nerng ; Chen, Hsin Fu. / Comparative global immune-related gene profiling of somatic cells, human pluripotent stem cells and their derivatives : Implication for human lymphocyte proliferation. In: Experimental and Molecular Medicine. 2017 ; Vol. 49, No. 9.
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AU - Wu, Chia Eng

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AU - Chou, Wen Hsi

AU - Lu, Chen Yu

AU - Ghelfi, Elisa

AU - Wu, Fang Chun

AU - Jan, Pey Shynan

AU - Huang, Mei Chi

AU - Allard, Patrick

AU - Lin, Shau Ping

AU - Ho, Hong Nerng

AU - Chen, Hsin Fu

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AB - 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. r The Author(s) 2017.

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