Germ cells: ENCODE’s forgotten cell type

2021 ◽  
Author(s):  
John R McCarrey ◽  
Keren Cheng
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Somatic Cell ◽  
Germ Cells ◽  
Developmental Stages ◽  
Cell Types ◽  
Recent Effort ◽  
Cell Type ◽  
Male And Female ◽  
Genome Wide

Abstract More than a decade ago, the ENCODE and NIH Epigenomics Roadmap consortia organized large multi-laboratory efforts to profile the epigenomes of >110 different mammalian somatic cell types. This generated valuable publicly accessible datasets that are being mined to reveal genome-wide patterns of a variety of different epigenetic parameters. This consortia approach facilitated the powerful and comprehensive multiparametric integrative analysis of the epigenomes in each cell type. However, no germ cell types were included among the cell types characterized by either of these consortia. Thus, comprehensive epigenetic profiling data is not generally available for the most evolutionarily important cells, male and female germ cells. We discuss the need for reproductive biologists to generate similar multiparametric epigenomic profiling datasets for both male and female germ cells at different developmental stages, and summarize our recent effort to derive such data for mammalian spermatogonial stem cells and progenitor spermatogonia.

scholarly journals Abnormal Meiosis Initiation in Germ Cell Caused by Aberrant Differentiation of Gonad Somatic Cell

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Min Chen ◽  
Min Chen ◽  
Suren Chen ◽  
Jingjing Zhou ◽  
Fangfang Dong ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Germ Cell ◽  
Somatic Cell ◽  
Germ Cells ◽  
Somatic Cells ◽  
Ectopic Expression ◽  
Genital Ridge ◽  
Male And Female ◽  
Germ Cell Differentiation ◽  
Exact Function

The interaction between germ cell and somatic cell plays important roles in germ cell development. However, the exact function of gonad somatic cell in germ cell differentiation is unclear. In the present study, the function of gonad somatic cell in germ cell meiosis was examined by using mouse models with aberrant somatic cell differentiation. In Wt1R394W/R394W mice, the genital ridge is absent due to the apoptosis of coelomic epithelial cells. Interestingly, in both male and female Wt1R394W/R394W germ cells, STRA8 was detected at E12.5 and the scattered SYCP3 foci were observed at E13.5 which was consistent with control females. In Wt1-/flox; Cre-ERTM mice, Wt1 was inactivated by the injection of tamoxifen at E9.5 and the differentiation of Sertoli and granulosa cells was completely blocked. We found that most germ cells were located outside of genital ridge after Wt1 inactivation. STRA8, SYCP3, and γH2AX proteins were detected in germ cells of both male and female Wt1-/flox; Cre-ERTM gonads, whereas no thread-like SYCP3 signal was observed. Our study demonstrates that aberrant development of gonad somatic cells leads to ectopic expression of meiosis-associated genes in germ cells, but meiosis was arrested before prophase I. These results suggest that the proper differentiation of gonad somatic cells is essential for germ cell meiosis.

scholarly journals Expression Profiling of Mammalian Male Meiosis and Gametogenesis Identifies Novel Candidate Genes for Roles in the Regulation of Fertility

2004 ◽  
Vol 15 (3) ◽  
pp. 1031-1043 ◽  
Author(s):  
Ulrich Schlecht ◽  
Philippe Demougin ◽  
Reinhold Koch ◽  
Leandro Hermida ◽  
Christa Wiederkehr ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Expression Profiling ◽  
Large Scale ◽  
Developmental Stages ◽  
Expression Patterns ◽  
Control Cell ◽  
Cell Types ◽  
Male Meiosis ◽  
Cell Expression

We report a comprehensive large-scale expression profiling analysis of mammalian male germ cells undergoing mitotic growth, meiosis, and gametogenesis by using high-density oligonucleotide microarrays and highly enriched cell populations. Among 11,955 rat loci investigated, 1268 were identified as differentially transcribed in germ cells at subsequent developmental stages compared with total testis, somatic Sertoli cells as well as brain and skeletal muscle controls. The loci were organized into four expression clusters that correspond to somatic, mitotic, meiotic, and postmeiotic cell types. This work provides information about expression patterns of ∼200 genes known to be important during male germ cell development. Approximately 40 of those are included in a group of 121 transcripts for which we report germ cell expression and lack of transcription in three somatic control cell types. Moreover, we demonstrate the testicular expression and transcriptional induction in mitotic, meiotic, and/or postmeiotic germ cells of 293 as yet uncharacterized transcripts, some of which are likely to encode factors involved in spermatogenesis and fertility. This group also contains potential germ cell-specific targets for innovative contraceptives. A graphical display of the data is conveniently accessible through the GermOnline database at http://www.germonline.org .

scholarly journals A sex-specific number of germ cells in embryonic gonads of Drosophila

Development ◽  
1995 ◽  
Vol 121 (6) ◽  
pp. 1867-1873 ◽  
Author(s):  
M. Poirie ◽  
E. Niederer ◽  
M. Steinmann-Zwicky
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Developmental Stages ◽  
Control Mechanism ◽  
Cell Number ◽  
Male And Female ◽  
First Instar ◽  
Specific Number ◽  
Specific Control ◽  
Time Point

Male first instar larvae possess more germ cells in their gonads than female larvae of the same stage. To determine the earliest time point of sexual dimorphism in germ cell number, we have counted the germ cells of sexed embryos at different developmental stages. We found no difference in germ cell number of male and female embryos at the blastoderm and early gastrulation stage, or when germ cells are about to exit the midgut pocket. We find, however, that males have significantly more germ cells than females as soon as the germ cells are near the places where the gonads are formed and in all later stages. Our results show that germ cells are subject to a sex-specific control mechanism that regulates the number of germ cells already in embryos.

scholarly journals Germline sexual fate is determined by the antagonistic action of dmrt1 and foxl3/foxl2 in tilapia

Development ◽  
2021 ◽  
pp. dev.199380
Author(s):  
Shengfei Dai ◽  
Shuangshuang Qi ◽  
Xueyan Wei ◽  
Xingyong Liu ◽  
Yibing Li ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Germ Cell ◽  
Somatic Cell ◽  
Cell Fate ◽  
Germ Cells ◽  
Sex Reversal ◽  
Testicular Development ◽  
Antagonistic Action ◽  
Male And Female ◽  
Fate Decision

Germline sexual fate has long been believed to be determined by the somatic environment, but this idea is challenged by recent studies of foxl3 mutants in medaka. Here we demonstrate that the sexual fate of tilapia germline is determined by the antagonistic interaction of dmrt1 and foxl3, which are transcriptionally repressed in male and female germ cells, respectively. Loss of dmrt1 rescued the germ cell sex reversal in foxl3Δ7/Δ7 XX fish, and loss of foxl3 partially rescued germ cell sex reversal but not somatic cell fate in dmrt1Δ5/Δ5 XY fish. Interestingly, germ cells lost sexual plasticity in dmrt1Δ5/Δ5 XY and foxl3Δ7/Δ7 XX single mutants, as aromatase inhibitor and estrogen treatment failed to rescue the respective phenotypes. However, recovery of germ cell sexual plasticity was observed in dmrt1/foxl3 double mutants. Importantly, mutation of somatic cell specific foxl2 resulted in testicular development in foxl3Δ7/Δ7 or dmrt1Δ5/Δ5 mutants. Our findings demonstrate that sexual plasticity of germ cells relies on the presence of both dmrt1 and foxl3. The existence of dmrt1 and foxl3 allows environmental factors to influence the sex fate decision in vertebrates.

scholarly journals The reversible developmental unipotency of germ cells in chicken

Reproduction ◽  
2010 ◽  
Vol 139 (1) ◽  
pp. 113-119 ◽  
Author(s):  
Jin Gyoung Jung ◽  
Young Mok Lee ◽  
Jin Nam Kim ◽  
Tae Min Kim ◽  
Ji Hye Shin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Germ Cells ◽  
Developmental Stages ◽  
Production Systems ◽  
Primordial Germ Cells ◽  
Transmission Efficiency ◽  
Germline Transmission ◽  
Adult Testis

We recently developed bimodal germline chimera production approaches by transfer of primordial germ cells (PGCs) or embryonic germ cells (EGCs) into embryos and by transplantation of spermatogonial stem cells (SSCs) or germline stem cells (GSCs) into adult testes. This study was undertaken to investigate the reversible developmental unipotency of chicken germ cells using our established germline chimera production systems. First, we transferred freshly isolated SSCs from adult testis or in vitro cultured GSCs into stage X and stage 14–16 embryos, and we found that these transferred SSCs/GSCs could migrate to the recipient embryonic gonads. Of the 527 embryos that received SSCs or GSCs, 135 yielded hatchlings. Of 17 sexually mature males (35.3%), six were confirmed as germline chimeras through testcross analysis resulting in an average germline transmission efficiency of 1.3%. Second, PGCs/EGCs, germ cells isolated from embryonic gonads were transplanted into adult testes. The EGC transplantation induced germline transmission, whereas the PGC transplantation did not. The germline transmission efficiency was 12.5 fold higher (16.3 vs 1.3%) in EGC transplantation into testis (EGCs to adult testis) than that in SSC/GSC transfer into embryos (testicular germ cells to embryo stage). In conclusion, chicken germ cells from different developmental stages can (de)differentiate into gametes even after the germ cell developmental clock is set back or ahead. Use of germ cell reversible unipotency might improve the efficiency of germ cell-mediated germline transmission.

scholarly journals Absence of mDazl produces a final block on germ cell development at meiosis

Reproduction ◽  
2003 ◽  
pp. 589-597 ◽  
Author(s):  
PT Saunders ◽  
JM Turner ◽  
M Ruggiu ◽  
M Taggart ◽  
PS Burgoyne ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Meiotic Prophase ◽  
Rna Binding ◽  
Developmental Stages ◽  
Cell Loss ◽  
Functional Differentiation ◽  
Autosomal Gene ◽  
Fetal Life ◽  
Male And Female

The autosomal gene DAZL is a member of a family of genes (DAZL, DAZ, BOULE), all of which contain a consensus RNA binding domain and are expressed in germ cells. Adult male and female mice null for Dazl lack gametes. In order to define more precisely the developmental stages in germ cells that require Dazl expression, the patterns of germ cell loss in immature male and female wild-type (+/+, WT) and Dazl -/- (DazlKO) mice were analysed. In females, loss of germ cells occurred during fetal life and was coincident with progression of cells through meiotic prophase. In males, testes were recovered from WT and DazlKO males obtained before and during the first wave of spermatogenesis (days 2-19). Mitotically active germ cells were present up to and including day 19. Functional differentiation of spermatogonia associated with detection of c-kit positive cells did not depend upon expression of Dazl. RBMY-positive cells (A, intermediate, B spermatogonia, zygotene and preleptotene spermatocytes) were reduced in DazlKO compared with WT testes. Staining of cell squashes from day 19 testes with anti-gamma-H2AX and anti-SCP3 antibodies showed that germ cells from DazlKO males were unable to progress beyond the leptotene stage of meiotic prophase I. It was concluded that in the absence of Dazl, germ cells can complete mitosis, and embark on functional differentiation but that, in both sexes, progression through meiotic prophase requires this RNA binding protein.

scholarly journals Characterization of Alternative Splicing (AS) Events during Chicken (Gallus gallus) Male Germ-Line Stem Cell Differentiation with Single-Cell RNA-seq

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1469
Author(s):  
Changhua Sun ◽  
Kai Jin ◽  
Qisheng Zuo ◽  
Hongyan Sun ◽  
Jiuzhou Song ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Alternative Splicing ◽  
Cell Differentiation ◽  
Germ Cell ◽  
Germ Cells ◽  
Germ Line ◽  
Rna Seq ◽  
Germ Cell Differentiation ◽  
Genome Wide

Alternative splicing (AS) is a ubiquitous, co-transcriptional, and post-transcriptional regulation mechanism during certain developmental processes, such as germ cell differentiation. A thorough understanding of germ cell differentiation will help us to open new avenues for avian reproduction, stem cell biology, and advances in medicines for human consumption. Here, based on single-cell RNA-seq, we characterized genome-wide AS events in manifold chicken male germ cells: embryonic stem cells (ESCs), gonad primordial germ cells (gPGCs), and spermatogonia stem cells (SSCs). A total of 38,494 AS events from 15,338 genes were detected in ESCs, with a total of 48,955 events from 14,783 genes and 49,900 events from 15,089 genes observed in gPGCs and SSCs, respectively. Moreover, this distribution of AS events suggests the diverse splicing feature of ESCs, gPGCs, and SSCs. Finally, several crucial stage-specific genes, such as NANOG, POU5F3, LIN28B, BMP4, STRA8, and LHX9, were identified in AS events that were transmitted in ESCs, gPGCs, and SSCs. The gene expression results of the RNA-seq data were validated by qRT-PCR. In summary, we provided a comprehensive atlas of the genome-wide scale of the AS event landscape in male chicken germ-line cells and presented its distribution for the first time. This research may someday improve treatment options for men suffering from male infertility.

scholarly journals A Germ Cell-specific Gene, Prmt5, Works in Somatic Cell Reprogramming

2011 ◽  
Vol 286 (12) ◽  
pp. 10641-10648 ◽  
Author(s):  
Go Nagamatsu ◽  
Takeo Kosaka ◽  
Miyuri Kawasumi ◽  
Taisuke Kinoshita ◽  
Keiyo Takubo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Somatic Cell ◽  
Germ Cells ◽  
Pluripotent Stem Cells ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
Cell Reprogramming ◽  
Specific Gene ◽  
Somatic Cell Reprogramming

Germ cells possess the unique ability to acquire totipotency during development in vivo as well as give rise to pluripotent stem cells under the appropriate conditions in vitro. Recent studies in which somatic cells were experimentally converted into pluripotent stem cells revealed that genes expressed in primordial germ cells (PGCs), such as Oct3/4, Sox2, and Lin28, are involved in this reprogramming. These findings suggest that PGCs may be useful for identifying factors that successfully and efficiently reprogram somatic cells into toti- and/or pluripotent stem cells. Here, we show that Blimp-1, Prdm14, and Prmt5, each of which is crucial for PGC development, have the potential to reprogram somatic cells into pluripotent stem cells. Among them, Prmt5 exhibited remarkable reprogramming of mouse embryonic fibroblasts into which Prmt5, Klf4, and Oct3/4 were introduced. The resulting cells exhibited pluripotent gene expression, teratoma formation, and germline transmission in chimeric mice, all of which were indistinguishable from those induced with embryonic stem cells. These data indicate that some of the factors that play essential roles in germ cell development are also active in somatic cell reprogramming.

scholarly journals Male germline stem cells in non-human primates

2017 ◽  
Vol 4 (2) ◽  
pp. 173-184 ◽  
Author(s):  
Swati Sharma ◽  
Joana M. D. Portela ◽  
Daniel Langenstroth-Röwer ◽  
Joachim Wistuba ◽  
Nina Neuhaus ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Germ Cells ◽  
Developmental Stages ◽  
Expression Patterns ◽  
Regulatory Mechanisms ◽  
Primate Species ◽  
Germline Stem Cells ◽  
Germline Development ◽  
Human Primate

Abstract. Over the past few decades, several studies have attempted to decipher the biology of mammalian germline stem cells (GSCs). These studies provide evidence that regulatory mechanisms for germ cell specification and migration are evolutionarily conserved across species. The characteristics and functions of primate GSCs are highly distinct from rodent species; therefore the findings from rodent models cannot be extrapolated to primates. Due to limited availability of human embryonic and testicular samples for research purposes, two non-human primate models (marmoset and macaque monkeys) are extensively employed to understand human germline development and differentiation. This review provides a broader introduction to the in vivo and in vitro germline stem cell terminology from primordial to differentiating germ cells. Primordial germ cells (PGCs) are the most immature germ cells colonizing the gonad prior to sex differentiation into testes or ovaries. PGC specification and migratory patterns among different primate species are compared in the review. It also reports the distinctions and similarities in expression patterns of pluripotency markers (OCT4A, NANOG, SALL4 and LIN28) during embryonic developmental stages, among marmosets, macaques and humans. This review presents a comparative summary with immunohistochemical and molecular evidence of germ cell marker expression patterns during postnatal developmental stages, among humans and non-human primates. Furthermore, it reports findings from the recent literature investigating the plasticity behavior of germ cells and stem cells in other organs of humans and monkeys. The use of non-human primate models would enable bridging the knowledge gap in primate GSC research and understanding the mechanisms involved in germline development. Reported similarities in regulatory mechanisms and germ cell expression profile in primates demonstrate the preclinical significance of monkey models for development of human fertility preservation strategies.

scholarly journals GC-1 spg cells are most similar to Leydig cells, a testis somatic cell-type, and not germ cells

2021 ◽  
Author(s):  
Andrew R Norman ◽  
Lauren Byrnes ◽  
Jeremy R Reiter
Keyword(s):  
Germ Cell ◽  
Somatic Cell ◽  
Cell Line ◽  
Germ Cells ◽  
Leydig Cells ◽  
Adult Mouse ◽  
Somatic Cells ◽  
Cell Type ◽  
Immortalized Cell ◽  
Somatic Cell Type

GC-1 spg is an immortalized cell line derived from an adult mouse testis and reported to be most similar to spermatocytes, a male germ cell-type. However, immunofluorescence indicates that GC-1 spg cells express WT1, a marker of testis somatic cells, and do not express markers of germ cells. Transcriptomic profiling indicate GC-1 cells are most similar to Leydig cells. Therefore, we conclude that GC-1 spg cells are most similar to testis somatic cells.

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