Gamete derivation from embryonic stem cells, induced pluripotent stem cells or somatic cell nuclear transfer-derived embryonic stem cells: state of the art.
Gamete derivation from embryonic stem cells, induced pluripotent stem cells or somatic cell nuclear transfer-derived embryonic stem cells: state of the art.
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DOI：
10.1071/rd14317
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发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Schatten G
中科院分区：
文献类型：
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作者：
Easley CA;Simerly CR;Schatten G
从多能干细胞（PSC）产生配子有许多科学依据和一些生物医学原理。在这里，我们考虑了从小鼠和灵长类动物（人类和非人类）的 PSC 中获取配子的几种策略及其预期的优势、挑战和局限性。尽管将凡人体细胞谱系与潜在永生生殖细胞系分开的“魏斯曼屏障”早已存在，但首先在小鼠和现在在人类中取得的突破是从体细胞中人为地创造生殖细胞。据报道，在小鼠中具有完全生殖活力的精子可以产生多代看似正常的后代，在人类中，已经获得了具有正确亲本印记的单倍体精子细胞。使用小鼠 PSC 在体外分化为原始生殖细胞，然后在异种移植重建人工卵巢后进行培养，在制造卵母细胞方面也取得了类似的进展。人工制造人类卵母细胞的进展被证明具有挑战性。这些人工配子的有用性，从评估环境暴露毒性到优化医疗治疗以防止对生育力的负面脱靶影响，可能被证明是无价的，就像配子发生的基本机制的基本发现一样。
Generating gametes from pluripotent stem cells (PSCs) has many scientific justifications and several biomedical rationales. Here, we consider several strategies for deriving gametes from PSCs from mice and primates (human and non-human) and their anticipated strengths, challenges and limitations. Although the ‘Weismann barrier’, which separates the mortal somatic cell lineages from the potentially immortal germline, has long existed, breakthroughs first in mice and now in humans are artificially creating germ cells from somatic cells. Spermatozoa with full reproductive viability establishing multiple generations of seemingly normal offspring have been reported in mice and, in humans, haploid spermatids with correct parent-of-origin imprints have been obtained. Similar progress with making oocytes has been published using mouse PSCs differentiated in vitro into primordial germ cells, which are then cultured after xenografting reconstructed artificial ovaries. Progress in making human oocytes artificially is proving challenging. The usefulness of these artificial gametes, from assessing environmental exposure toxicity to optimising medical treatments to prevent negative off-target effects on fertility, may prove invaluable, as may basic discoveries on the fundamental mechanisms of gametogenesis.