Diagnosing spermatogonial stemness.
Diagnosing spermatogonial stemness.
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诊断精原干性。
DOI：
10.1095/biolreprod.115.129890
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发表时间：
2015
影响因子：
3.6
通讯作者：
Hamra,FKent
中科院分区：
文献类型：
--
作者：
Hamra,FKent
家族健康在很大程度上反映了祖先卵母细胞和精子传递的性状的质量。这一生命事实赋予了产生配子的生殖细胞对可遗传基因组结构的健康的内在责任[1]。因此，生殖细胞中检测到的DNA突变频率低于体细胞，这反映了保持基因组完整性的压力[2-4]。在哺乳动物中，自我更新的生殖系干细胞被认为是生殖生命中雄性性腺所特有的。这是因为有丝分裂的雌性生殖细胞在哺乳动物的性别决定后不久进入减数分裂以分化成卵母细胞，这发生在胚胎发生的中途[5]。卵母细胞阻滞和选择性卵母细胞变性被假设为提供额外的保护措施，保护生殖系免受基因组异常的影响，突出了“女性保护模型”[6，7]。相比之下，雄性生殖系干细胞，称为“精原干细胞”，通过在胚胎和成人生命中相对较长的时间内进行有丝分裂自我更新来维持睾丸中精子的产生。50年的人类[8]。因此，全基因组测序提供的证据表明，生殖细胞复制其DNA的时间的性别依赖性增加与长期观察到的“男性突变偏好”密切相关[9-11]。在大多数物种中，我们明确鉴定精原细胞复制功能作为生殖系干细胞的能力尚未得到牢固确立，但这种假设似乎是理解缓冲生殖系可传播DNA突变积累的细胞机制的基础[12，13]。科学家们正在迅速注释啮齿动物的干细胞和祖细胞精原细胞[14-17]，这些进展正在转化为其他哺乳动物物种，包括灵长类[18-23]。在临床上，诊断精原干细胞基因组稳定性的能力似乎至关重要，以便安全地将其与计划生育和遗传医学的巨大潜在益处联系起来[24]。
Familial health largely reflects the quality of traits transmitted by ancestral oocytes and spermatozoa. This fact of life endows gamete-producing germ cells with an intrinsic accountability for the well-being of heritable genomic architecture [1]. Consequently, it is fitting that pressure to preserve genomic integrity is reflected by lower frequencies of DNA mutations detected in germ cells than in somatic cells [2–4]. In mammals, self-renewing germline stem cells are considered unique to male gonads during reproductive life. This is because mitotically dividing female germ cells enter meiosis to differentiate into oocytes shortly after sex determination in mammals, which occurs midway through embryogenesis [5]. Oogenic arrests, together with selective oocyte degeneration, are hypothesized to provide additional safeguards that defend the germline from genomic abnormalities, highlighting the ‘‘female-protective model’’[6, 7]. In contrast, male germline stem cells, termed ‘‘spermatogonial stem cells,’’sustain spermatozoan production in testes by mitotically self-renewing over relatively long periods that span both embryonic and adult life (. 50 years in humans)[8]. Accordingly, whole-genome sequencing is providing evidence that sex-dependent increases in time given for a germline to replicate its DNA correlate strongly with longstanding observations of ‘‘male mutation bias’’[9–11]. In most species, our ability to unequivocally identify spermatogonia that replicate to function as germline stem cells has yet to be firmly established, but such a hypothesis appears fundamental to understanding cellular mechanisms that buffer the accumulation of transmittable DNA mutations by germlines [12, 13]. Scientists are rapidly annotating stem and progenitor spermatogonia in rodents [14–17], and these advances are being translated to other mammalian species, including primates [18–23]. Clinically, the ability to diagnose genomic stability in spermatogonial stem cells seems paramount in order to safely make the connection to their enormous prospective benefits for family planning and genetic medicine [24].