Heterozygous embryonic stem cell lines derived from nonhuman primate parthenotes
Heterozygous embryonic stem cell lines derived from nonhuman primate parthenotes
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DOI：
10.1634/stemcells.2007-0869
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发表时间：
2008-01-01
期刊：
影响因子：
5.2
通讯作者：
Mitalipov, Shoukhrat
中科院分区：
文献类型：
--
作者：
Dighe, Vikas;Clepper, Lisa;Mitalipov, Shoukhrat
单亲单性动物代表了组织相容性干细胞的潜在来源，其应与卵母细胞供体同基因，因此适合用于细胞或组织替代疗法。我们生成了五种恒河猴孤雌胚胎干细胞（PESC）系，它们具有稳定的二倍体雌性核型，在形态上与双亲对照没有区别，表达关键的多能标记，并在体内和体外分化后生成代表所有三个胚层的细胞衍生物。有趣的是，在卵母细胞供体中大多数多态性位点观察到高水平的杂合性。一些 PESC 系在主要组织相容性复合体区域也是杂合的，携带与卵子供体雌性相同的单倍型。表达分析揭示了一些印记基因的转录本，这些基因通常仅从父本等位基因表达。这些结果表明，PESC 衍生表型在再生医学中潜在应用的局限性，包括异常基因组印记和高水平纯合性，是细胞系依赖性的，并且并不总是存在。 PESC 细胞系的产量足够高，足以实用，其衍生物适合自体移植到卵母细胞供体中，或者可用于为广泛的患者建立组织相容性细胞系库。
Monoparental parthenotes represent a potential source of histocompatible stem cells that should be isogenic with the oocyte donor and therefore suitable for use in cell or tissue replacement therapy. We generated five rhesus monkey parthenogenetic embryonic stem cell (PESC) lines with stable, diploid female karyotypes that were morphologically indistinguishable from biparental controls, expressed key pluripotent markers, and generated cell derivatives representative of all three germ layers following in vivo and in vitro differentiation. Interestingly, high levels of heterozygosity were observed at the majority of loci that were polymorphic in the oocyte donors. Some PESC lines were also heterozygous in the major histocompatibility complex region, carrying haplotypes identical to those of the egg donor females. Expression analysis revealed transcripts from some imprinted genes that are normally expressed from only the paternal allele. These results indicate that limitations accompanying the potential use of PESC-derived phenotypes in regenerative medicine, including aberrant genomic imprinting and high levels of homozygosity, are cell line-dependent and not always present. PESC lines were derived in high enough yields to be practicable, and their derivatives are suitable for autologous transplantation into oocyte donors or could be used to establish a bank of histocompatible cell lines for a broad spectrum of patients.