Studying human reproductive biology through single-cell analysis and in vitro differentiation of stem cells into germ cell-like cells
Studying human reproductive biology through single-cell analysis and in vitro differentiation of stem cells into germ cell-like cells
复制标题
通过单细胞分析和干细胞体外分化为生殖细胞样细胞来研究人类生殖生物学。
DOI：
10.1093/humupd/dmaa021
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发表时间：
2020-09-01
影响因子：
13.3
通讯作者：
Kee, Kehkooi
中科院分区：
文献类型：
--
作者：
Li, Lin;Yang, Risako;Kee, Kehkooi
背景人类生殖发育的分子和细胞机制一直受到人类样本稀缺和伦理限制的限制。近年来，人类多能干细胞体外分化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独特的机制开辟了新的途径。目的和原理本综述的目的是整理这些新方法的新发现和有洞察力的发现，旨在介绍研究人员和临床医生使用这些工具来研究人类生殖生物学和开发治疗不育症的方法。搜索期包括从2000年到现在的所有文献。对人性腺的单细胞分析已经在不同发育阶段和细胞亚群中发现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，研究人员使用了人类多能细胞体外分化为生殖细胞的方法，并证实了一些遗传要求在人类生殖细胞中是独一无二的，在小鼠模型中不是保守的。此外，这些研究还阐明了性腺中转录调控网络以及生殖细胞和体细胞之间的相互作用。单细胞分析的广泛意义使研究人员能够利用有限的临床样本来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工具，以检查这些新识别的基因标记，并研究以前与不孕症相关的突变的致病作用。结合这两种方法，研究人员可以确定在人类生殖发育中必不可少的和独特的基因标记和网络，从而产生更准确的诊断工具，用于评估生殖障碍和开发不孕不育的治疗方法。
BACKGROUND 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.OBJECTIVE AND RATIONALE 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.SEARCH METHODS 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.OUTCOMES 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.WIDER IMPLICATIONS 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.