Lin Li1, Risako Yang2, Chenghong Yin1, Kehkooi Kee3. 1. Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Chaoyang, Beijing 100026, China. 2. Department of Biology, Colgate University, Hamilton, NY 13346, USA. 3. Department of Basic Medical Sciences, Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China.
Abstract
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.
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.
Authors: Swati Mishra; Jasin Taelman; Yolanda W Chang; Annekatrien Boel; Petra De Sutter; Björn Heindryckx; Susana M Chuva De Sousa Lopes Journal: Cells Date: 2021-05-16 Impact factor: 6.600
Authors: Swati Mishra; Jasin Taelman; Mina Popovic; Laurentijn Tilleman; Evi Duthoo; Margot van der Jeught; Dieter Deforce; Filip van Nieuwerburgh; Björn Menten; Petra de Sutter; Annekatrien Boel; Susana M Chuva De Sousa Lopes; Björn Heindryckx Journal: Stem Cells Date: 2021-02-02 Impact factor: 6.277