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Development (Cambridge, England) Mar 2021The peri-implantation window of mammalian development is the crucial window for primordial germ cell (PGC) specification. Whereas pre-implantation dynamics are... (Review)
Review
The peri-implantation window of mammalian development is the crucial window for primordial germ cell (PGC) specification. Whereas pre-implantation dynamics are relatively conserved between species, the implantation window marks a stage of developmental divergence between key model organisms, and thus potential variance in the cell and molecular mechanisms for PGC specification. In humans, PGC specification is very difficult to study To address this, the combined use of human and nonhuman primate embryos, and stem cell-based embryo models are essential for determining the origin of PGCs, as are comparative analyses to the equivalent stages of mouse development. Understanding the origin of PGCs in the peri-implantation embryo is crucial not only for accurate modeling of this essential process using stem cells, but also in determining the role of global epigenetic reprogramming upon which sex-specific differentiation into gametes relies.
Topics: Animals; Cell Differentiation; DNA Methylation; Embryonic Development; Embryonic Stem Cells; Germ Cells; Humans; Models, Biological; X Chromosome
PubMed: 33722957
DOI: 10.1242/dev.189217 -
Current Topics in Developmental Biology 2019Germ cells undergo epigenome reprogramming for proper development of the next generation. The achievement of in vitro germ cell derivation from human and mouse... (Review)
Review
Germ cells undergo epigenome reprogramming for proper development of the next generation. The achievement of in vitro germ cell derivation from human and mouse pluripotent stem cells and further differentiation in a plane culture and in aggregation with gonadal somatic cells offers unprecedented opportunities for investigation of the germ cell development. Moreover, advances in low-input/single-cell genomics have enabled detailed investigation of epigenome dynamics during germ cell development. These technologies have advanced our knowledge of epigenome reprogramming during the specification and development of primordial germ cells, their sex differentiation, and gametogenesis. Key findings include details of chromatin remodeling and transcriptional regulation, progressive and comprehensive DNA demethylation, and tight links between DNA demethylation and histone marks during the development of primordial germ cells, acquisition of unique totipotent epigenome during oogenesis (e.g., broad H3K4me3 domains and low-level three-dimensional genomic organization), and unexpected organization of the sperm genome. Moreover, these studies suggest the importance of epigenome analyses for in-depth evaluations of in vitro gametogenesis.
Topics: Animals; Cellular Reprogramming; Chromatin Assembly and Disassembly; DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Germ Cells; Humans
PubMed: 31155364
DOI: 10.1016/bs.ctdb.2019.04.005 -
Cell Aug 2011The generation of properly functioning gametes in vitro requires reconstitution of the multistepped pathway of germ cell development. We demonstrate here the generation...
The generation of properly functioning gametes in vitro requires reconstitution of the multistepped pathway of germ cell development. We demonstrate here the generation of primordial germ cell-like cells (PGCLCs) in mice with robust capacity for spermatogenesis. PGCLCs were generated from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) through epiblast-like cells (EpiLCs), a cellular state highly similar to pregastrulating epiblasts but distinct from epiblast stem cells (EpiSCs). Reflecting epiblast development, EpiLC induction from ESCs/iPSCs is a progressive process, and EpiLCs highly competent for the PGC fate are a transient entity. The global transcription profiles, epigenetic reprogramming, and cellular dynamics during PGCLC induction from EpiLCs meticulously capture those associated with PGC specification from the epiblasts. Furthermore, we identify Integrin-Ī²3 and SSEA1 as markers that allow the isolation of PGCLCs with spermatogenic capacity from tumorigenic undifferentiated cells. Our findings provide a paradigm for the first step of in vitro gametogenesis.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Embryonic Stem Cells; Gene Expression Profiling; Germ Cells; Germ Layers; Induced Pluripotent Stem Cells; Mice; Pluripotent Stem Cells; Spermatogenesis
PubMed: 21820164
DOI: 10.1016/j.cell.2011.06.052 -
Cells Jul 2021Assisted reproductive technologies (ARTs) have developed considerably in recent years; however, they cannot rectify germ cell aplasia, such as non-obstructive... (Review)
Review
Assisted reproductive technologies (ARTs) have developed considerably in recent years; however, they cannot rectify germ cell aplasia, such as non-obstructive azoospermia (NOA) and oocyte maturation failure syndrome. In vitro gametogenesis is a promising technology to overcome infertility, particularly germ cell aplasia. Early germ cells, such as primordial germ cells, can be relatively easily derived from pluripotent stem cells (PSCs); however, further progression to post-meiotic germ cells usually requires a gonadal niche and signals from gonadal somatic cells. Here, we review the recent advances in in vitro male and female germ cell derivation from PSCs and discuss how this technique is used to understand the biological mechanism of gamete development and gain insight into its application in infertility.
Topics: Animals; Cells, Cultured; Female; Fertility; Gametogenesis; Germ Cells; Humans; Infertility; Male; Oogenesis; Ovum; Pluripotent Stem Cells; Reproductive Techniques, Assisted; Spermatogenesis; Spermatogonia
PubMed: 34440657
DOI: 10.3390/cells10081889 -
Seminars in Cell & Developmental Biology Apr 2020In many organisms, primordial germ cells (PGCs) are specified at a different location than where the gonad forms, meaning that PGCs must migrate toward the gonad within... (Review)
Review
In many organisms, primordial germ cells (PGCs) are specified at a different location than where the gonad forms, meaning that PGCs must migrate toward the gonad within the early developing embryo. Following species-specific paths, PGCs can be passively carried by surrounding tissues and also perform active migration. When PGCs actively migrate through and along a variety of embryonic structures in different organisms, they adopt an ancestral robust migration mode termed "amoeboid motility", which allows cells to migrate within diverse environments. In this review, we discuss the possible significance of the PGC migration process in facilitating the evolution of animal body shape. In addition, we summarize the latest findings relevant for the molecular and cellular mechanisms controlling the movement and the directed migration of PGCs in different species.
Topics: Animals; Cell Movement; Germ Cells; Humans
PubMed: 31864795
DOI: 10.1016/j.semcdb.2019.11.015 -
Development (Cambridge, England) Apr 2021In each generation, the germline is tasked with producing somatic lineages that form the body, and segregating a population of cells for gametogenesis. During animal... (Review)
Review
In each generation, the germline is tasked with producing somatic lineages that form the body, and segregating a population of cells for gametogenesis. During animal development, when do cells of the germline irreversibly commit to producing gametes? Integrating findings from diverse species, we conclude that the final commitment of the germline to gametogenesis - the process of germ cell determination - occurs after primordial germ cells (PGCs) colonize the gonads. Combining this understanding with medical findings, we present a model whereby germ cell tumors arise from cells that failed to undertake germ cell determination, regardless of their having colonized the gonads. We propose that the diversity of cell types present in these tumors reflects the broad developmental potential of migratory PGCs.
Topics: Animals; Cell Differentiation; Cell Movement; Gametogenesis; Germ Cells; Humans; Models, Biological; Neoplasms, Germ Cell and Embryonal
PubMed: 33913479
DOI: 10.1242/dev.198150 -
Advances in Experimental Medicine and... 2017Two unique characteristics of the germ line are the ability to persist from generation to generation and to retain full developmental potential while differentiating... (Review)
Review
Two unique characteristics of the germ line are the ability to persist from generation to generation and to retain full developmental potential while differentiating into gametes. How the germ line is specified that allows it to retain these characteristics within the context of a developing embryo remains unknown and is one focus of current research. Germ cell specification proceeds through one of two basic mechanisms: cell autonomous or inductive. Here, we discuss how germ plasm driven germ cell specification (cell autonomous) occurs in both zebrafish and the frog Xenopus. We describe the segregation of germ cells during embryonic development of solitary and colonial ascidians to provide an evolutionary context to both mechanisms. We conclude with a discussion of the inductive mechanism as exemplified by both the mouse and axolotl model systems. Regardless of mechanism, several general themes can be recognized including the essential role of repression and posttranscriptional regulation of gene expression.
Topics: Animals; Cell Differentiation; Embryonic Development; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Germ Cells; Mice; Xenopus; Xenopus laevis; Zebrafish
PubMed: 27975276
DOI: 10.1007/978-3-319-46095-6_8 -
International Journal of Molecular... Feb 2021In the present era, infertility is one of the major issues which restricts many couples to have their own children. Infertility is the inability to achieve a clinical... (Review)
Review
In the present era, infertility is one of the major issues which restricts many couples to have their own children. Infertility is the inability to achieve a clinical pregnancy after regular unprotected sexual intercourse for the period of one year or more. Various factors including defective male or female germ cell development, unhealthy and improper lifestyles, diseases like cancer and associated chemo-or-radiation therapies, congenital disorders, etc., may be responsible for infertility. Therefore, it is highly important to understand the basic concepts of germ cell development including primordial germ cell (PGC) formation, specification, migration, entry to genital ridges and their molecular mechanisms, activated pathways, paracrine and autocrine signaling, along with possible alteration which can hamper germ cell development and can cause adversities like cancer progression and infertility. Knowing all these aspects in a proper way can be very much helpful in improving our understanding about gametogenesis and finding possible ways to cure related disorders. Here in this review, various aspects of gametogenesis especially female gametes and relevant factors causing functional impairment have been thoroughly discussed.
Topics: Animals; Carcinogenesis; Epigenesis, Genetic; Female; Germ Cells; Humans; Neoplasms, Germ Cell and Embryonal; Oocytes
PubMed: 33671303
DOI: 10.3390/ijms22041979 -
Biology of Reproduction Sep 2019Germ cell development is a series of highly specialized processes through which diploid pluripotent cells differentiate into haploid gametes. The processes include... (Review)
Review
Germ cell development is a series of highly specialized processes through which diploid pluripotent cells differentiate into haploid gametes. The processes include biologically important events such as epigenetic reprogramming, sex determination, and meiosis. The mechanisms underlying these events are key issues in reproductive and developmental biology, yet they still remain elusive. As a tool to elucidate these mechanisms, in vitro gametogenesis, which reproduces germ cell development in culture, has long been sought for decades. Recently, methods of in vitro gametogenesis have undergone rapid development in association with stem cell biology, opening many possibilities in this field. This new technology is considered an alternative source of gametes for the reproduction of animals and perhaps humans. This review summarizes current advances and problems in in vitro gametogenesis.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Embryonic Stem Cells; Female; Gametogenesis; Germ Cells; Humans; Inventions; Male
PubMed: 31295346
DOI: 10.1093/biolre/ioz111 -
Current Topics in Developmental Biology 2019Germ cells are the stem cells of the species. Thus, it is critical that we have a good understanding of how they are specified, how the somatic cells instruct and... (Review)
Review
Germ cells are the stem cells of the species. Thus, it is critical that we have a good understanding of how they are specified, how the somatic cells instruct and support them, how they commit to one or other sex, and how they ultimately develop into functional gametes. Here, we focus on specifics of how sexual fate is determined during fetal life. Because the majority of relevant experimental work has been done using the mouse model, we focus on that species. We review evidence regarding the identity of instructive signals from the somatic cells, and the molecular responses that occur in germ cells in response to those extrinsic signals. In this way we aim to clarify progress to date regarding the mechanisms underlying the mitotic to meiosis switch in germ cells of the fetal ovary, and those involved in adopting and securing male fate in germ cells of the fetal testis.
Topics: Animals; Cell Differentiation; Female; Germ Cells; Male; Mammals; Meiosis; Mice; Oogenesis; Sex Characteristics; Sex Determination Processes; Signal Transduction; Spermatogenesis
PubMed: 30999978
DOI: 10.1016/bs.ctdb.2019.01.011