Expression of major histocompatibility complex class I proteins and their antigen processing chaperones in mouse embryonic stem cells from fertilized and parthenogenetic embryos.
Expression of major histocompatibility complex class I proteins and their antigen processing chaperones in mouse embryonic stem cells from fertilized and parthenogenetic embryos.
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DOI：
10.1111/j.1399-0039.2008.01132.x
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发表时间：
2008-11
期刊：
影响因子：
--
通讯作者：
Warner CM
中科院分区：
文献类型：
--
作者：
Lampton PW;Crooker RJ;Newmark JA;Warner CM
胚胎干细胞是一种多能细胞，具有分化为可用于移植治疗的细胞或组织的潜力。孤雌生殖胚胎干细胞最近从小鼠和人的卵母细胞中分离出来，有望成为与供体卵母细胞组织相容的细胞来源。由于主要组织相容性复合体(MHC)抗原在介导组织排斥或接受中的重要性，我们检测了来自受精(FES)和孤雌生殖(PES)胚胎的小鼠胚胎干细胞中MHC I类蛋白以及几种MHC I类抗原加工和递呈伴侣蛋白的mRNA和蛋白表达水平。我们发现H-2K、Qa-2、TAP1、TAP2和Tapasin在未分化和分化的ES细胞中都有低水平的表达，并在分化后14天被干扰素-γ(干扰素-γ)显著上调。同样，在分化14d后，干扰素-γ可上调H-2kb和H-2Kk蛋白的表达，但Qa-2蛋白的表达仍然很低或不表达。我们还发现，与T细胞相比，MHC I类、TAP1、TAP2和Tapasin mRNAs在ES细胞中的表达水平都非常低，这表明这些基因在ES细胞中的转录调控。Calnexin是一种伴侣分子，参与MHC以外的其他途径的表达，在ES细胞和T细胞中的表达水平相似，在ES细胞中不被干扰素-γ上调。总体而言，来自受精胚胎和孤雌胚胎的胚胎干细胞在mRNA和蛋白质水平上表现出非常相似的基因表达模式。FES和PES细胞系在MHC I类分子表达和抗原处理机制方面的相似性为孤雌生殖ES细胞在移植治疗中的潜在应用提供了证据。
Embryonic stem (ES) cells are pluripotent cells with the potential to differentiate into cells or tissues that may be used for transplantation therapy. Parthenogenetic ES cells have been recently derived from both mouse and human oocytes and hold promise as a cell source which is histocompatible to the oocyte donor. Due to the importance of major histocompatibility complex (MHC) antigens in mediating tissue rejection or acceptance, we examined levels of mRNA and protein expression of MHC class I proteins, as well as several MHC class I antigen processing and presentation chaperones, in mouse embryonic stem cells derived from both fertilized (fES) and parthenogenetic (pES) embryos. We found that H-2K, Qa-2, TAP1, TAP2 and tapasin mRNAs were all expressed at low levels in undifferentiated and differentiating ES cells, and were significantly upregulated in response to interferon-γ (IFN-γ) treatment following 14 days of differentiation. Likewise, expression of H-2Kb and H-2Kk proteins were upregulated to detectable levels by IFN-γ after 14 days of differentiation, but Qa-2 protein expression remained low or absent. We also found that MHC class I, TAP1, TAP2, and tapasin mRNAs were all expressed at very low levels in ES cells compared to T cells, suggesting transcriptional regulation of these genes in ES cells. Calnexin, a chaperone molecule involved in other pathways than MHC expression, had mRNA levels that were similar in ES cells and T cells, and was not upregulated by IFN-γ in ES cells. Overall, embryonic stem cells derived from fertilized embryos and parthenogenetic embryos displayed remarkably similar patterns of gene expression at the mRNA and protein levels. The similarity between the fES and pES cell lines in regard to expression of MHC class I and antigen processing machinery provides evidence for the potential usefulness of parthenogenetic ES cells in transplantation therapy.
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影响因子：
9.2
作者：
Munsie, MJ;Michalska, AE;Mountford, PS
通讯作者：
Mountford, PS
影响因子：
5.3
作者：
Keirstead, HS;Nistor, G;Steward, O
通讯作者：
Steward, O
DOI：
10.1084/jem.134.1.83
发表时间：
1971-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cudkowicz G;Bennett M
通讯作者：
Bennett M
影响因子：
5.2
作者：
Li, L;Baroja, ML;Bhatia, M
通讯作者：
Bhatia, M
影响因子：
2.7
作者：
Comiskey, Martina;Domino, Kenneth E.;Warner, Carol M.
通讯作者：
Warner, Carol M.