1 Department of Biology, Laboratory for Aging and Infertility Research, Northeastern University , Boston, Massachusetts.
2 Department of Chemistry & Chemical Biology, The Barnett Institute for Chemical and Biological Analysis, Northeastern University , Boston, Massachusetts.
Stem Cells Dev. 2018 Jun 1;27(11):723-735. doi: 10.1089/scd.2018.0002. Epub 2018 May 29.
The in vivo gene networks involved in coordinating human fetal ovarian development remain obscure. In this study, quantitative mass spectrometry was conducted on ovarian tissue collected at key stages during the first two trimesters of human gestational development, confirming the expression profiling data using immunofluorescence, as well as in vitro modeling with human oogonial stem cells (OSCs) and human embryonic stem cells (ESCs). A total of 3,837 proteins were identified in samples spanning developmental days 47-137. Bioinformatics clustering and Ingenuity Pathway Analysis identified DNA mismatch repair and base excision repair as major pathways upregulated during this time. In addition, MAEL and TEX11, two key meiosis-related proteins, were identified as highly expressed during the developmental window associated with fetal oogenesis. These findings were confirmed and extended using in vitro differentiation of OSCs into in vitro derived oocytes and of ESCs into primordial germ cell-like cells and oocyte-like cells, as models. In conclusion, the global protein expression profiling data generated by this study have provided novel insights into human fetal ovarian development in vivo and will serve as a valuable new resource for future studies of the signaling pathways used to orchestrate human oogenesis and folliculogenesis.
在体内协调人类胎儿卵巢发育的基因网络仍然不清楚。在这项研究中,对人类妊娠发育头两个三个月期间关键阶段采集的卵巢组织进行了定量质谱分析,通过免疫荧光法和人卵原干细胞(OSC)和人胚胎干细胞(ESC)的体外建模,证实了表达谱数据。在跨越发育日 47-137 的样本中鉴定出了 3837 种蛋白质。生物信息学聚类和Ingenuity Pathway Analysis 鉴定出 DNA 错配修复和碱基切除修复是在此期间上调的主要途径。此外,在与胎儿卵发生相关的发育窗口期间,鉴定出 MAEL 和 TEX11 这两种关键的减数分裂相关蛋白高度表达。这些发现通过体外分化 OSCs 为体外衍生的卵母细胞和 ESC 为原始生殖细胞样细胞和卵母细胞样细胞得到了证实和扩展,这些细胞作为模型。总之,本研究产生的全局蛋白质表达谱数据为体内人类胎儿卵巢发育提供了新的见解,并将成为未来研究用于协调人类卵发生和卵泡发生的信号通路的宝贵新资源。