scholarly journals Epigenetic Regulation during Primordial Germ Cell Development and Differentiation

2021 ◽  
pp. 1-21
Author(s):  
Navin B. Ramakrishna ◽  
Keir Murison ◽  
Eric A. Miska ◽  
Harry G. Leitch
Keyword(s):  
Germ Cell ◽  
Epigenetic Regulation ◽  
Critical Period ◽  
Current Knowledge ◽  
Primordial Germ Cell ◽  
Future Research ◽  
Epigenetic Alterations ◽  
Germline Development ◽  
Development And Differentiation ◽  
Non Coding Rnas

Germline development varies significantly across metazoans. However, mammalian primordial germ cell (PGC) development has key conserved landmarks, including a critical period of epigenetic reprogramming that precedes sex-specific differentiation and gametogenesis. Epigenetic alterations in the germline are of unique importance due to their potential to impact the next generation. Therefore, regulation of, and by, the non-coding genome is of utmost importance during these epigenomic events. Here, we detail the key chromatin changes that occur during mammalian PGC development and how these interact with the expression of non-coding RNAs alongside broader epitranscriptomic changes. We identify gaps in our current knowledge, in particular regarding epigenetic regulation in the human germline, and we highlight important areas of future research.

scholarly journals Emerging role of a novel small non-coding regulatory RNA: tRNA-derived small RNA

ExRNA ◽  
2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Fangfang Jin ◽  
Zhigang Guo
Keyword(s):  
Small Rna ◽  
Current Knowledge ◽  
Future Research ◽  
Regulatory Rna ◽  
Biological Functions ◽  
Research Directions ◽  
Non Coding Rna ◽  
Future Research Directions ◽  
Non Coding Rnas

Abstract The discovery of small non-coding RNAs, such as miRNA and piRNA, has dramatically changed our understanding of the role RNA plays in organisms. Recent studies show that a novel small non-coding RNA generated from cleavage of tRNA or pre-tRNA, called tRNA-derived small RNA (tsRNA), serves as a new regulator of gene expression. tsRNA has been determined participate in regulating some specific physiological and pathological processes. Although knowledge regarding the biological roles of miRNA and piRNA is expanding, whether tsRNAs play similar roles remains poorly understood. Here, we review the current knowledge regarding the mechanisms of action and biological functions of tsRNAs in intracellular, extracellular and intergenerational inheritance, and highlight the potential application of tsRNAs in human diseases, and present the current problems and future research directions.

piRNA identification based on motif discovery

2014 ◽  
Vol 10 (12) ◽  
pp. 3075-3080 ◽  
Author(s):  
Xiuqin Liu ◽  
Jun Ding ◽  
Fuzhou Gong
Keyword(s):  
Epigenetic Regulation ◽  
Motif Discovery ◽  
Germline Development ◽  
Transposon Silencing ◽  
Non Coding Rnas

Piwi-interacting RNA (piRNA) is a class of small non-coding RNAs about 24 to 32 nucleotides long, associated with PIWI proteins, which are involved in germline development, transposon silencing, and epigenetic regulation.

scholarly journals Maternal Piwi Regulates Primordial Germ Cell Development to Ensure the Fertility of Female Progeny in Drosophila

Genetics ◽  
2021 ◽  
Author(s):  
Lauren E Gonzalez ◽  
Xiongzhuo Tang ◽  
Haifan Lin
Keyword(s):  
Germ Cell ◽  
Primordial Germ Cell ◽  
Early Embryo ◽  
Null Alleles ◽  
Germline Stem Cell ◽  
Germline Development ◽  
Female Progeny ◽  
Adult Ovary ◽  
Pirna Pathway ◽  
Germline Sex Determination

Abstract In many animals, germline development is initiated by proteins and RNAs that are expressed maternally. PIWI proteins and their associated small noncoding PIWI-interacting RNAs (piRNAs), which guide PIWI to target RNAs by base-pairing, are among the maternal components deposited into the germline of the Drosophila early embryo. Piwi has been extensively studied in the adult ovary and testis, where it is required for transposon suppression, germline stem cell self-renewal, and fertility. Consequently, loss of Piwi in the adult ovary using piwi-null alleles or knockdown from early oogenesis results in complete sterility, limiting investigation into possible embryonic functions of maternal Piwi. In this study, we show that the maternal Piwi protein persists in the embryonic germline through gonad coalescence, suggesting that maternal Piwi can regulate germline development beyond early embryogenesis. Using a maternal knockdown strategy, we find that maternal Piwi is required for the fertility and normal gonad morphology of female, but not male, progeny. Following maternal piwi knockdown, transposons were mildly derepressed in the early embryo but were fully repressed in the ovaries of adult progeny. Furthermore, the maternal piRNA pool was diminished, reducing the capacity of the PIWI/piRNA complex to target zygotic genes during embryogenesis. Examination of embryonic germ cell proliferation and ovarian gene expression showed that the germline of female progeny was partially masculinized by maternal piwi knockdown. Our study reveals a novel role for maternal Piwi in the germline development of female progeny and suggests that the PIWI/piRNA pathway is involved in germline sex determination in Drosophila.

scholarly journals Generation of Primordial Germ Cell-like Cells from iPSCs Derived from Turner Syndrome Patients

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3099
Author(s):  
Aline Fernanda de Souza ◽  
Fabiana Fernandes Bressan ◽  
Naira Caroline Godoy Pieri ◽  
Ramon Cesar Botigelli ◽  
Tamas Revay ◽  
...  
Keyword(s):  
Germ Cell ◽  
Turner Syndrome ◽  
Genetic Disorder ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Cell Formation ◽  
In Vitro Models ◽  
Germline Development ◽  
Germ Cell Specification

Turner syndrome (TS) is a genetic disorder in females with X Chromosome monosomy associated with highly variable clinical features, including premature primary gonadal failure leading to ovarian dysfunction and infertility. The mechanism of development of primordial germ cells (PGCs) and their connection with ovarian failure in TS is poorly understood. An in vitro model of PGCs from TS would be beneficial for investigating genetic and epigenetic factors that influence germ cell specification. Here we investigated the potential of reprogramming peripheral mononuclear blood cells from TS women (PBMCs-TS) into iPSCs following in vitro differentiation in hPGCLCs. All hiPSCs-TS lines demonstrated pluripotency state and were capable of differentiation into three embryonic layers (ectoderm, endoderm, and mesoderm). The PGCLCs-TS recapitulated the initial germline development period regarding transcripts and protein marks, including the epigenetic profile. Overall, our results highlighted the feasibility of producing in vitro models to help the understanding of the mechanisms associated with germ cell formation in TS.

scholarly journals Testing the role of SOX15 in human primordial germ cell fate

2019 ◽  
Vol 4 ◽  
pp. 122
Author(s):  
Merrick Pierson Smela ◽  
Anastasiya Sybirna ◽  
Frederick C.K. Wong ◽  
M. Azim Surani
Keyword(s):  
Flow Cytometry ◽  
Germ Cell ◽  
Primordial Germ Cell ◽  
Mechanistic Study ◽  
Germline Development ◽  
Cell Identity ◽  
Protein Levels ◽  
Germ Cell Specification ◽  
The Impact ◽  
Early Human

Background: Potentially novel regulators of early human germline development have been identified recently, including SOX15 and SOX17, both of which show specific expression in human primordial germ cells. SOX17 is now known to be a critical specifier of human germ cell identity. There have been suggestions, as yet without evidence, that SOX15 might also play a prominent role. The early human germline is inaccessible for direct study, but an in vitro model of human primordial germ cell-like cell (hPGCLC) specification from human embryonic stem cells (hESCs) has been developed. This enables mechanistic study of human germ cell specification using genetic tools to manipulate the levels of SOX15 and SOX17 proteins to explore their roles in hPGCLC specification. Methods: SOX15 and SOX17 proteins were depleted during hPGCLC specification from hESCs using the auxin-inducible degron system, combined with a fluorescent reporter for tracking protein levels. Additionally, SOX15 protein was overexpressed using the ProteoTuner system. Protein-level expression changes were confirmed by immunofluorescence. The impact on hPGCLC specification efficiency was determined by flow cytometry at various time points. qPCR experiments were performed to determine some transcriptional effects of SOX15 perturbations. Results: We observed specific SOX15 expression in hPGCLCs by using immunofluorescence and flow cytometry analysis. Depletion of SOX15 had no significant effect on hPGCLC specification efficiency on day 4 after induction, but there was a significant and progressive decrease in hPGCLCs on days 6 and 8. By contrast, depletion of SOX17 completely abrogated hPGCLC specification. Furthermore, SOX15 overexpression resulted in a significant increase in hPGCLC fraction on day 8. qPCR analysis revealed a possible role for the germ cell and pluripotency regulator PRDM14 in compensating for changes to SOX15 protein levels. Conclusions: SOX17 is essential for hPGCLC specification, yet SOX15 is dispensable. However, SOX15 may have a role in maintaining germ cell identity.

Exosomal microRNAs in the development of essential hypertension and its potential as biomarkers

2021 ◽  
Author(s):  
Paulina Pei Suu Tan ◽  
Deborah Hall ◽  
William M. Chilian ◽  
Yook Chin Chia ◽  
Shamsul Mohd Zain ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Invasive Disease ◽  
Future Research ◽  
Circulating Mirnas ◽  
Disease Biomarkers ◽  
Non Invasive ◽  
Exosomal Mirnas ◽  
External Conditions ◽  
Hypertension Diagnosis ◽  
Non Coding Rnas

MicroRNAs (miRNAs) are small regulatory molecules that are involved in post-transcriptional modifications. These non-coding RNAs are usually ferried by extracellular carriers such as exosomes or other protein and lipid carriers inside a range of body fluids including plasma and urine. Due to their ability to withstand harsh external conditions, exosomal miRNAs possess enormous potentials as non-invasive disease biomarkers for, notably hypertension, whereby exosomal miRNAs have been implicated in its pathophysiological processes. More importantly, alterations in the microenvironment as a result of disease progression can induce active and selective loading of miRNAs into exosomes. In this paper, we first review the mechanisms of miRNA loading into exosomes, followed by the roles of exosomal miRNAs in the development of hypertension; and the potentials of exosomal miRNAs as biomarkers in comparison to other free circulating miRNAs. Finally challenges and future research surrounding exosomal miRNAs will also be discussed. The information synthesized in this review summarizes current knowledge of non-invasive biomarkers for early hypertension diagnosis and for probing therapeutic efficacy.

scholarly journals Epigenetics and the germline

Reproduction ◽  
2005 ◽  
Vol 129 (2) ◽  
pp. 137-149 ◽  
Author(s):  
Cinzia Allegrucci ◽  
Alexandra Thurston ◽  
Emma Lucas ◽  
Lorraine Young
Keyword(s):  
Current Knowledge ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Cell Lineage ◽  
Epigenetic Modifications ◽  
Germline Development ◽  
Genome Wide ◽  
Three Stages ◽  
Epigenetic Processes

Epigenetic processes affect three stages of germline development, namely (1) specification and formation of primordial germ cells and their germline derivatives through lineage-specific epigenetic modifications, in the same manner as other embryonic lineages are formed, (2) a largely genome-wide erasure and re-establishment of germline-specific epigenetic modifications that only occurs in the embryonic primordial germ cell lineage, followed by re-establishment of sex-specific patterns during gametogenesis, and (3) differential epigenetic modifications to the mature male and female gamete genomes shortly after fertilisation. This review will detail current knowledge of these three processes both at the genome-wide level and at specific imprinted loci. The consequences of epigenetic perturbation are discussed and newin vitromodels which may allow further understanding of a difficult developmental period to study, especially in the human, are highlighted.

scholarly journals Crosstalk between N6-methyladenosine modification and circular RNAs: current understanding and future directions

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xin Wang ◽  
Rui Ma ◽  
Xilin Zhang ◽  
Lian Cui ◽  
Yangfeng Ding ◽  
...  
Keyword(s):  
Molecular Biology ◽  
Essential Role ◽  
Current Knowledge ◽  
Current Understanding ◽  
Future Research ◽  
Circular Rnas ◽  
Future Directions ◽  
Research Perspectives ◽  
Non Coding Rnas ◽  
Rna Maturation

AbstractN6-methyladenosine (m6A) is a prevalent internal modification in eukaryotic RNAs regulated by the so-called “writers”, “erasers”, and “readers”. m6A has been demonstrated to exert critical molecular functions in modulating RNA maturation, localization, translation and metabolism, thus playing an essential role in cellular, developmental, and disease processes. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed single-stranded structures generated by back-splicing. CircRNAs also participate in physiological and pathological processes through unique mechanisms. Despite their discovery several years ago, m6A and circRNAs has drawn increased research interest due to advances in molecular biology techniques these years. Recently, several scholars have investigated the crosstalk between m6A and circRNAs. In this review, we provide an overview of the current knowledge of m6A and circRNAs, as well as summarize the crosstalk between these molecules based on existing research. In addition, we present some suggestions for future research perspectives.

scholarly journals A noncanonical role of NOD-like receptor NLRP14 in PGCLC differentiation and spermatogenesis

2020 ◽  
Vol 117 (36) ◽  
pp. 22237-22248
Author(s):  
Yike Yin ◽  
Shiyu Cao ◽  
Huancheng Fu ◽  
Xueying Fan ◽  
Jingfei Xiong ◽  
...  
Keyword(s):  
Germ Cell ◽  
Nuclear Translocation ◽  
Primordial Germ Cell ◽  
Male Mice ◽  
Germline Development ◽  
Severe Oligozoospermia ◽  
Knock Out ◽  
Germ Cell Differentiation

NOD-like receptors (NLRs) are traditionally recognized as major inflammasome components. The role of NLRs in germ cell differentiation and reproduction is not known. Here, we identified the gonad-specific Nlrp14 as a pivotal regulator in primordial germ cell-like cell (PGCLC) differentiation in vitro. Physiologically, knock out of Nlrp14 resulted in reproductive failure in both female and male mice. In adult male mice, Nlrp14 knockout (KO) inhibited differentiation of spermatogonial stem cells (SSCs) and meiosis, resulting in trapped SSCs in early stages, severe oligozoospermia, and sperm abnormality. Mechanistically, NLRP14 promoted spermatogenesis by recruiting a chaperone cofactor, BAG2, to bind with HSPA2 and form the NLRP14−HSPA2−BAG2 complex, which strongly inhibited ChIP-mediated HSPA2 polyubiquitination and promoted its nuclear translocation. Finally, loss of HSPA2 protection and BAG2 recruitment by NLRP14 was confirmed in a human nonsense germline variant associated with male sterility. Together, our data highlight a unique proteasome-mediated, noncanonical function of NLRP14 in PGCLC differentiation and spermatogenesis, providing mechanistic insights of gonad-specific NLRs in mammalian germline development.

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