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Pesquisa : A11.872.700.250.750 [Categoria DeCS]
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Texto completo SciELO Chile
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Id: biblio-950823
Autor: Chen, Haide; Li, Yang; Lin, Xijuan; Cui, Di; Cui, Chun; Li, Hui; Xiao, Lei.
Título: Functional disruption of human leukocyte antigen II in human embryonic stem cell
Fonte: Biol. Res;48:1-9, 2015. ilus, graf.
Idioma: en.
Projeto: Ministry of Agriculture; . National Natural Science Foundation of China; . Zhejiang Provincial Natural Science Foundation of China; . Agricultural Variety Breeding Project of Zhejiang Province; . Ministry of Science and Technology of China.
Resumo: BACKGROUND: Theoretically human embryonic stem cells (hESCs) have the capacity to self-renew and differentiate into all human cell types. Therefore, the greatest promise of hESCs-based therapy is to replace the damaged tissues of patients suffering from traumatic or degenerative diseases by the exact same type of cells derived from hESCs. Allo-graft immune rejection is one of the obstacles for hESCs-based clinical applications. Human leukocyte antigen (HLA) II leads to CD4+ T cells-mediated allograft rejection. Hence, we focus on optimizing hESCs for clinic application through gene modification. RESULTS: Transcription activator-like effector nucleases (TALENs) were used to target MHC class II transactivator (CIITA) in hESCs efficiently. CIITA(-/-)hESCs did not show any difference in the differentiation potential and self-renewal capacity. Dendritic cells (DCs) derived from CIITA(-/-)hESCs expressed CD83 and CD86 but without the constitutive HLA II. Fibroblasts derived from CIITA(-/-)hESCs were powerless in IFN-γ inducible expression of HLA II. CONCLUSION: We generated HLA II defected hESCs via deleting CIITA, a master regulator of constitutive and IFN-γ inducible expression of HLA II genes. CIITA(-/-)hESCs can differentiate into tissue cells with non-HLA II expression. It's promising that CIITA(-/-)hESCs-derived cells could be used in cell therapy (e.g., T cells and DCs) and escape the attack of receptors' CD4+ T cells, which are the main effector cells of cellular immunity in allograft.
Descritores: Proteínas Nucleares/genética
Diferenciação Celular/genética
Deleção de Genes
Células-Tronco Embrionárias Humanas/metabolismo
Células Dendríticas/metabolismo
Glicoproteínas de Membrana/metabolismo
Células Tumorais Cultivadas
Antígenos de Histocompatibilidade Classe II/genética
Antígenos CD/metabolismo
Interferon gama/metabolismo
Camundongos SCID
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Antígeno B7-2/metabolismo
Corpos Embrioides/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Autorrenovação Celular
Células Apresentadoras de Antígenos/metabolismo
Limites: Humanos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: CL1.1 - Biblioteca Central

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Texto completo SciELO Brasil
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Id: lil-573711
Autor: Yamada, Hiroya; Takano, Toru; Matsuzuka, Fumio; Watanabe, Mikio; Miyauchi, Akira; Iwatani, Yoshinori.
Título: Transcriptional activity of the 5'-flanking region of the thyroid transcription factor-1 gene in human thyroid cell lines
Fonte: Genet. mol. biol;34(1):6-10, 2011. ilus, tab.
Idioma: en.
Projeto: Princess Takamatsu Cancer Research Fund.
Resumo: Thyroid transcription factor-1 (TTF-1, NKX2-1) is a homeodomain-containing transcriptional factor that binds to and activates the promoters of thyroid and lung-specific genes, such as thyroglobulin, thyroid peroxidase, and thyroid stimulating hormone receptor. TTF-1 is known to play a key role in the development of the thyroid. However, the precise mechanism of TTF-1 gene transcription in human thyroid cells has not been studied. The expression of transcriptional activity in various lengths of the 5'-flanking region of the human TTF -1 gene was studied in TTF-1 positive and negative human thyroid cell lines. Increased transcriptional activity was observed in thyroid cell lines containing plasmids that coded for a sequence proximal to the transcription start site of exon 1 of the TTF-1 gene. However, we did not observe any difference in promoter activity in the region up to -2.6 kb from the proximal transcription start site of the TTF-1 gene between TTF-1 positive and negative cells. These results suggest that the proximal 5'-flanking region of the human TTF -1 gene does not contain sufficient cis-active regulatory information to direct gene expression in thyroid cells,and that other cis-or trans-acting factors participate in the thyroid specific gene expression of TTF-1.
Descritores: Células-Tronco Embrionárias Humanas
Fator de Transcrição STAT3
Glândula Tireoide
Limites: Humanos
Responsável: BR1.1 - BIREME

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