Transcription and imprinting dynamics in developing postnatal male germline stem cells.
Transcription and imprinting dynamics in developing postnatal male germline stem cells.
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转录和烙印动力学在发展产后男性系干细胞中。
DOI：
10.1101/gad.261925.115
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发表时间：
2015-11-01
影响因子：
10.5
通讯作者：
Cairns BR
中科院分区：
文献类型：
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作者：
Hammoud SS;Low DH;Yi C;Lee CL;Oatley JM;Payne CJ;Carrell DT;Guccione E;Cairns BR
Hammoud等人进行了广泛的基因组分析，并对幼鱼中三种广泛的精原干细胞（SSC）群体进行了分类：(1)上皮样SSC，(2)更丰富的间充质样SSC，以及(3)（在年龄较大的幼鱼中）丰富的配子发生细胞。间充质样ssc在父系印记位点缺乏印记，但在青春期前完全恢复了印记。间充质样ssc在减数分裂基因和某些单等位基因神经基因上也表现出发育相关的DNA去甲基化。出生后的精原干细胞（ssc）通过增殖和发育阶段的进展，在生殖精子发生之前填充睾丸生态位。为了更好地理解，我们在出生后的多个阶段对富含特定标记（THY1、KIT、OCT4、ID4或GFRa1）的亚群进行了广泛的基因组分析。总体而言，我们的研究表明，幼鱼的精原细胞有三大类：(1)上皮样精原细胞（THY1+，高OCT4、ID4和GFRa1），(2)更丰富的间充质样精原细胞（THY1+，中等OCT4和ID4，高间充质标记物），(3)（在年龄较大的幼鱼中）丰富的精原细胞参与配子形成（高KIT+）。上皮样精原细胞显示出预期的印记模式，但令人惊讶的是，间充质样精原细胞在父系印记位点缺乏印记，但在青春期前完全恢复了印记。此外，间充质样精原细胞在减数分裂基因和某些单等位基因神经基因（如原钙粘蛋白和嗅觉受体）上也显示出发育相关的DNA去甲基化。我们还揭示了新的候选受体配体网络，涉及ssc和发育中的生态位。综上所述，新生儿/幼崽含有异质上皮样或间充质样精子原细胞群体，后者显示出广泛的DNA甲基化/染色质动力学。我们推测这种可塑性有助于ssc在发育中的精小管内增殖和迁移，适当的生态位相互作用和膜附着使间充质样精原细胞亚型细胞恢复到具有正常印迹特征的上皮样状态。
Hammoud et al. conducted extensive genomic profiling and classified three broad spermatogonial stem cell (SSC) populations in juveniles: (1) epithelial-like SSCs, (2) more abundant mesenchymal-like SSCs, and (3) (in older juveniles) abundant cells committing to gametogenesis. Mesenchymal-like SSCs lacked imprinting specifically at paternally imprinted loci but fully restored imprinting prior to puberty. Mesenchymal-like SSCs also displayed developmentally linked DNA demethylation at meiotic genes and also at certain monoallelic neural genes. Postnatal spermatogonial stem cells (SSCs) progress through proliferative and developmental stages to populate the testicular niche prior to productive spermatogenesis. To better understand, we conducted extensive genomic profiling at multiple postnatal stages on subpopulations enriched for particular markers (THY1, KIT, OCT4, ID4, or GFRa1). Overall, our profiles suggest three broad populations of spermatogonia in juveniles: (1) epithelial-like spermatogonia (THY1+; high OCT4, ID4, and GFRa1), (2) more abundant mesenchymal-like spermatogonia (THY1+; moderate OCT4 and ID4; high mesenchymal markers), and (3) (in older juveniles) abundant spermatogonia committing to gametogenesis (high KIT+). Epithelial-like spermatogonia displayed the expected imprinting patterns, but, surprisingly, mesenchymal-like spermatogonia lacked imprinting specifically at paternally imprinted loci but fully restored imprinting prior to puberty. Furthermore, mesenchymal-like spermatogonia also displayed developmentally linked DNA demethylation at meiotic genes and also at certain monoallelic neural genes (e.g., protocadherins and olfactory receptors). We also reveal novel candidate receptor–ligand networks involving SSCs and the developing niche. Taken together, neonates/juveniles contain heterogeneous epithelial-like or mesenchymal-like spermatogonial populations, with the latter displaying extensive DNA methylation/chromatin dynamics. We speculate that this plasticity helps SSCs proliferate and migrate within the developing seminiferous tubule, with proper niche interaction and membrane attachment reverting mesenchymal-like spermatogonial subtype cells back to an epithelial-like state with normal imprinting profiles.