HLA-Matching Potential of an Established Human Embryonic Stem Cell Bank in China

Lin, Ge; Xie, Yubin; Ouyang, Qi; Qian, Xiaobing; Xie, Pingyuan; Zhou, Xiaoying; Xiong, Bo; Tan, Yue‐Qiu; Wen, Lan; Deng, Li; Zhou, Jing; Zhou, Di; Du, Lili; Cheng, Dehua; Liao, Yi; Gu, Yifan; Zhang, Shuoping; Liu, Tiancheng; Sun, Yi; Lu, Guangxiu

doi:10.1016/j.stem.2009.10.009

Cited by 90 publications

(64 citation statements)

References 21 publications

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“…The hESC and induced pluripotent stem cell (iPSC) line used in this study were established and cultured in our laboratory as described previously (17,18). Briefly, cells were cultured on a feeder layer of mitotically inactivated mouse embryonic fibroblasts.…”

Section: Methodsmentioning

confidence: 99%

Transcriptional Activation of Human CDCA8 Gene Regulated by Transcription Factor NF-Y in Embryonic Stem Cells and Cancer Cells

Dai

Miao

et al. 2015

Journal of Biological Chemistry

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Background:The regulation of CDCA8 gene expression remains unclear. Results: CDCA8 promoter is activated in hESCs and cancer cells, in which NF-Y is a positive-regulator by binding to the CCAAT-box. Conclusion: CDCA8 is transcriptionally activated in hESCs and cancer cells and is positively regulated by NF-Y. Significance: Characterization of CDCA8 regulation provides a better understanding of its biological functions.

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Section: Methodsmentioning

confidence: 99%

Transcriptional Activation of Human CDCA8 Gene Regulated by Transcription Factor NF-Y in Embryonic Stem Cells and Cancer Cells

Dai

Miao

et al. 2015

Journal of Biological Chemistry

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“…The hESC lines were obtained from the established hESC bank at our center (Lin et al, 2009). The blastocysts used in this study were collected from patients receiving in vitro fertilization treatment.…”

Section: Sample Preparationmentioning

confidence: 99%

Telomerase-mediated telomere elongation from human blastocysts to embryonic stem cells

Zeng¹,

Liu²,

Sun³

et al. 2014

Development

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High telomerase activity is a characteristic of human embryonic stem cells (hESCs), however, the regulation and maintenance of correct telomere length in hESCs is unclear. In this study we investigated telomere elongation in hESCs in vitro and found that telomeres lengthened from their derivation in blastocysts through early expansion, but stabilized at later passages. We report that the core unit of telomerase, hTERT, was highly expressed in hESCs in blastocysts and throughout long-term culture; furthermore, this was regulated in a Wnt-b-catenin-signaling-dependent manner. Our observations that the alternative lengthening of telomeres (ALT) pathway was suppressed in hESCs and that hTERT knockdown partially inhibited telomere elongation, demonstrated that high telomerase activity was required for telomere elongation. We observed that chromatin modification through trimethylation of H3K9 and H4K20 at telomeric regions decreased during early culture. This was concurrent with telomere elongation, suggesting that epigenetic regulation of telomeric chromatin may influence telomerase function. By measuring telomere length in 96 hESC lines, we were able to establish that telomere length remained relatively stable at 12.0261.01 kb during later passages (15-95). In contrast, telomere length varied in hESCs with genomic instability and hESC-derived teratomas. In summary, we propose that correct, stable telomere length may serve as a potential biomarker for genetically stable hESCs.

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“…iPS-derived cells or tissues will more probably, at least in part, be transplanted in an allogeneic setting. Therefore, efforts are currently being undertaken to establish both hESC (Lin et al, 2009) and iPS cell banks (Tamaoki et al, 2010) in order to achieve at least partial HLA matching and reduce the risk for rejection. However, immunosuppressive protocols might still be needed at various levels.…”

Section: Introductionmentioning

confidence: 99%

Immunobiology of naïve and genetically modified HLA-class-I-knockdown human embryonic stem cells

Deuse

Seifert

Phillips

et al. 2011

Journal of Cell Science

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KD was followed by flow cytometry and showed levels between 1% and 12% of those of naïve hESC between days 7 and 42 (means ± s.e.m.). (b) A total of 10 6 hESCs or hESC KD were transplanted into the gastrocnemius muscle of either immunocompetent Balb/c or severely immunocompromised SCID-beige mice. All ten Balb/c mice rapidly rejected the hESC transplants, whereas the cells survived in ten SCID-beige recipients. Rejection of hESC KD was markedly attenuated and four out of ten hESC KD grafts achieved long-term survival. 4128 Author Correction The first author apologises for these errors.Immunobiology of naïve and genetically modified HLA-class-I-knockdown human embryonic stem cells SummaryHuman embryonic stem cells (hESCs) can serve as a universal cell source for emerging cell or tissue replacement strategies, but immune rejection of hESC derivatives remains an unsolved problem. Here, we sought to describe the mechanisms of rejection for naïve hESCs and upon HLA class I (HLA I) knockdown (hESC KD ). hESCs were HLA I-positive but negative for HLA II and co-stimulatory molecules. Transplantation of naïve hESC into immunocompetent Balb/c mice induced substantial T helper cell 1 and 2 (Th1 and Th2) responses with rapid cell death, but hESCs survived in immunodeficient SCID-beige recipients. Histology revealed mainly macrophages and T cells, but only scattered natural killer (NK) cells. A surge of hESC-specific antibodies against hESC class I, but not class II antigens, was observed. Using HLA I RNA interference and intrabody technology, HLA I surface expression of hESC KD was 88%-99% reduced. T cell activation after hESC KD transplantation into Balb/c was significantly diminished, antibody production was substantially alleviated, the levels of graft-infiltrating immune cells were reduced and the survival of hESC KD was prolonged. Because of their very low expression of stimulatory NK ligands, NK-susceptibility of naïve hESCs and hESC KD was negligible. Thus, HLA I recognition by T cells seems to be the primary mechanism of hESC recognition, and T cells, macrophages and hESC-specific antibodies participate in hESC killing.

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HLA-Matching Potential of an Established Human Embryonic Stem Cell Bank in China

Cited by 90 publications

References 21 publications

Transcriptional Activation of Human CDCA8 Gene Regulated by Transcription Factor NF-Y in Embryonic Stem Cells and Cancer Cells

Transcriptional Activation of Human CDCA8 Gene Regulated by Transcription Factor NF-Y in Embryonic Stem Cells and Cancer Cells

Telomerase-mediated telomere elongation from human blastocysts to embryonic stem cells

Immunobiology of naïve and genetically modified HLA-class-I-knockdown human embryonic stem cells

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