Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Chaoyang, Beijing 100026, China.
Department of Biology, Colgate University, Hamilton, NY 13346, USA.
Hum Reprod Update. 2020 Sep 1;26(5):670-688. doi: 10.1093/humupd/dmaa021.
Understanding the molecular and cellular mechanisms of human reproductive development has been limited by the scarcity of human samples and ethical constraints. Recently, in vitro differentiation of human pluripotent stem cells into germ cells and single-cell analyses have opened new avenues to directly study human germ cells and identify unique mechanisms in human reproductive development.
The goal of this review is to collate novel findings and insightful discoveries with these new methodologies, aiming at introducing researchers and clinicians to the use of these tools to study human reproductive biology and develop treatments for infertility.
PubMed was used to search articles and reviews with the following main keywords: in vitro differentiation, human stem cells, single-cell analysis, spermatogenesis, oogenesis, germ cells and other key terms related to these subjects. The search period included all publications from 2000 until now.
Single-cell analyses of human gonads have identified many important gene markers at different developmental stages and in subpopulations of cells. To validate the functional roles of these gene markers, researchers have used the in vitro differentiation of human pluripotent cells into germ cells and confirmed that some genetic requirements are unique in human germ cells and are not conserved in mouse models. Moreover, transcriptional regulatory networks and the interaction of germ and somatic cells in gonads were elucidated in these studies.
Single-cell analyses allow researchers to identify gene markers and potential regulatory networks using limited clinical samples. On the other hand, in vitro differentiation methods provide clinical researchers with tools to examine these newly identify gene markers and study the causative effects of mutations previously associated with infertility. Combining these two methodologies, researchers can identify gene markers and networks which are essential and unique in human reproductive development, thereby producing more accurate diagnostic tools for assessing reproductive disorders and developing treatments for infertility.
人类生殖发育的分子和细胞机制的研究受到人类样本稀缺和伦理限制的限制。最近，体外分化人类多能干细胞为生殖细胞和单细胞分析为直接研究人类生殖细胞和确定人类生殖发育中的独特机制开辟了新途径。
本综述的目的是整理这些新方法的新发现和有见地的发现，旨在向研究人员和临床医生介绍使用这些工具研究人类生殖生物学和开发治疗不孕不育症的方法。
使用 PubMed 搜索以下主要关键词的文章和综述：体外分化、人类干细胞、单细胞分析、精子发生、卵子发生、生殖细胞和与这些主题相关的其他关键词。搜索期包括从 2000 年至今的所有出版物。
对人类性腺的单细胞分析在不同发育阶段和细胞亚群中确定了许多重要的基因标记。为了验证这些基因标记的功能作用，研究人员使用体外分化人类多能细胞为生殖细胞，并证实了一些遗传要求在人类生殖细胞中是独特的，在小鼠模型中并不保守。此外，在这些研究中还阐明了转录调控网络和生殖细胞与体细胞在性腺中的相互作用。
单细胞分析允许研究人员使用有限的临床样本识别基因标记和潜在的调控网络。另一方面，体外分化方法为临床研究人员提供了研究这些新鉴定基因标记和研究先前与不孕相关的突变的因果效应的工具。将这两种方法结合起来，研究人员可以识别在人类生殖发育中必不可少和独特的基因标记和网络，从而为评估生殖障碍和开发不孕不育症治疗方法提供更准确的诊断工具。
