scholarly journals Zebrafish dazl regulates cystogenesis upstream of the meiotic transition and germline stem cell specification and independent of meiotic checkpoints

2019 ◽  
Author(s):  
Sylvain Bertho ◽  
Mara Clapp ◽  
Torsten U. Banisch ◽  
Jan Bandemer ◽  
Erez Raz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Rna Binding ◽  
Process Analysis ◽  
Cyst Formation ◽  
Germline Stem Cell ◽  
Germline Stem Cells ◽  
Asymmetric Divisions ◽  
Germline Cyst ◽  
Deleted In Azoospermia

AbstractFertility and gamete reserves are maintained by asymmetric divisions of the germline stem cells to produce new stem cells or daughters that differentiate as gametes. Before entering meiosis, differentiating germ cells (GCs) of sexual animals typically undergo cystogenesis. This evolutionary conserved process involves synchronous and incomplete mitotic divisions of a germ cell daughter (cystoblast) to generate sister cells connected by stable intercellular bridges that facilitate exchange of materials to support a large synchronous population of gamete progenitors. Here we investigate cystogenesis in zebrafish and identified Deleted in azoospermia (Dazl), a conserved vertebrate RNA binding protein as a regulator of this process. Analysis of dazl mutants revealed an essential role for Dazl in regulating incomplete cytokinesis and germline cyst formation before the meiotic transition. Accordingly, dazl mutant GCs form defective ring canals, and ultimately remain as individual cells that fail to differentiate as meiocytes. In addition to promoting cystoblast divisions and meiotic entry, dazl function is required upstream of germline stem cell establishment and fertility.Summary StatementWe show that zebrafish dazl is required for incomplete cytokinesis to generate germline cysts during cystogenesis, acts upstream of germline stem cell establishment, and is required for meiosis, and fertility.

scholarly journals Zebrafish dazl regulates cystogenesis and germline stem cell specification during the primordial germ cell to germline stem cell transition

Development ◽  
2021 ◽  
Vol 148 (7) ◽  
Author(s):  
Sylvain Bertho ◽  
Mara Clapp ◽  
Torsten U. Banisch ◽  
Jan Bandemer ◽  
Erez Raz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Rna Binding ◽  
Process Analysis ◽  
Primordial Germ Cell ◽  
Cyst Formation ◽  
Rapid Expansion ◽  
Germline Stem Cell ◽  
Cell Specification ◽  
Ring Canals

ABSTRACT Fertility and gamete reserves are maintained by asymmetric divisions of the germline stem cells to produce new stem cells or daughters that differentiate as gametes. Before entering meiosis, differentiating germ cells (GCs) of sexual animals typically undergo cystogenesis. This evolutionarily conserved process involves synchronous and incomplete mitotic divisions of a GC daughter (cystoblast) to generate sister cells connected by intercellular bridges that facilitate the exchange of materials to support rapid expansion of the gamete progenitor population. Here, we investigated cystogenesis in zebrafish and found that early GCs are connected by ring canals, and show that Deleted in azoospermia-like (Dazl), a conserved vertebrate RNA-binding protein (Rbp), is a regulator of this process. Analysis of dazl mutants revealed the essential role of Dazl in regulating incomplete cytokinesis, germline cyst formation and germline stem cell specification before the meiotic transition. Accordingly, dazl mutant GCs form defective ring canals, and ultimately remain as individual cells that fail to differentiate as meiocytes. In addition to promoting cystoblast divisions and meiotic entry, dazl is required for germline stem cell establishment and fertility.

Nanos and Pumilio have critical roles in the development and function of Drosophila germline stem cells

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 679-690 ◽  
Author(s):  
A. Forbes ◽  
R. Lehmann
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Germ Cells ◽  
Rna Binding ◽  
Drosophila Embryo ◽  
Germline Stem Cell ◽  
Germline Stem Cells ◽  
Embryonic Patterning ◽  
Germline Development ◽  
Egg Chambers

The zinc-finger protein Nanos and the RNA-binding protein Pumilio act together to repress the translation of maternal hunchback RNA in the posterior of the Drosophila embryo, thereby allowing abdomen formation. nanos RNA is localized to the posterior pole during oogenesis and the posteriorly synthesized Nanos protein is sequestered into the germ cells as they form in the embryo. This maternally provided Nanos protein is present in germ cells throughout embryogenesis. Here we show that maternally deposited Nanos protein is essential for germ cell migration. Lack of zygotic activity of nanos and pumilio has a dramatic effect on germline development of homozygous females. Given the coordinate function of nanos and pumilio in embryonic patterning, we analyzed the role of these genes in oogenesis. We find that both genes act in the germline. Although the nanos and pumilio ovarian phenotypes have similarities and both genes ultimately affect germline stem cell development, the focus of these phenotypes appears to be different. While pumilio mutant ovaries fail to maintain stem cells and all germline cells differentiate into egg chambers, the focus of nanos function seems to lie in the differentiation of the stem cell progeny, the cystoblast. Consistent with the model that nanos and pumilio have different phenotypic foci during oogenesis, we detect high levels of Pumilio protein in the germline stem cells and high levels of Nanos in the dividing cystoblasts. We therefore suggest that, in contrast to embryonic patterning, Nanos and Pumilio may interact with different partners in the germline.

scholarly journals CENP-C regulates centromere assembly, asymmetry and epigenetic age in Drosophila germline stem cells

2020 ◽  
Author(s):  
Ben L Carty ◽  
Anna A Dattoli ◽  
Elaine M Dunleavy
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Germ Line ◽  
Asymmetric Distribution ◽  
Germline Stem Cells ◽  
Daughter Cells ◽  
Sister Chromatids ◽  
Asymmetric Divisions ◽  
Centromere Assembly

AbstractGermline stem cells divide asymmetrically to produce one new daughter stem cell and one daughter cell that will subsequently undergo meiosis and differentiate to generate the mature gamete. The silent sister hypothesis proposes that in asymmetric divisions, the selective inheritance of sister chromatids carrying specific epigenetic marks between stem and daughter cells impacts cell fate. To facilitate this selective inheritance, the hypothesis specifically proposes that the centromeric region of each sister chromatid is distinct. In Drosophila germ line stem cells (GSCs), it has recently been shown that the centromeric histone CENP-A (called CID in flies) - the epigenetic determinant of centromere identity - is asymmetrically distributed between sister chromatids. In these cells, CID deposition occurs in G2 phase such that sister chromatids destined to end up in the stem cell harbour more CENP-A, assemble more kinetochore proteins and capture more spindle microtubules. These results suggest a potential mechanism of ‘mitotic drive’ that might bias chromosome segregation. Here we report that the inner kinetochore protein CENP-C, is required for the assembly of CID in G2 phase in GSCs. Moreover, CENP-C is required to maintain a normal asymmetric distribution of CID between stem and daughter cells. In addition, we find that CID is lost from centromeres in aged GSCs and that a reduction in CENP-C accelerates this loss. Finally, we show that CENP-C depletion in GSCs disrupts the balance of stem and daughter cells in the ovary, shifting GSCs toward a self-renewal tendency. Ultimately, we provide evidence that centromere assembly and maintenance via CENP-C is required to sustain asymmetric divisions in female Drosophila GSCs.

scholarly journals JNK signaling triggers spermatogonial dedifferentiation during chronic stress to maintain the germline stem cell pool in the Drosophila testis

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Salvador C Herrera ◽  
Erika A Bach
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Chronic Stress ◽  
Germline Stem Cell ◽  
Germline Stem Cells ◽  
Jnk Signaling ◽  
Cell Pool ◽  
Drosophila Testis ◽  
Bag Of Marbles ◽  
Stem Cell Pool

Exhaustion of stem cells is a hallmark of aging. In the Drosophila testis, dedifferentiated germline stem cells (GSCs) derived from spermatogonia increase during lifespan, leading to the model that dedifferentiation counteracts the decline of GSCs in aged males. To test this, we blocked dedifferentiation by mis-expressing the differentiation factor bag of marbles (bam) in spermatogonia while lineage-labeling these cells. Strikingly, blocking bam-lineage dedifferentiation under normal conditions in virgin males has no impact on the GSC pool. However, in mated males or challenging conditions, inhibiting bam-lineage dedifferentiation markedly reduces the number of GSCs and their ability to proliferate and differentiate. We find that bam-lineage derived GSCs have significantly higher proliferation rates than sibling GSCs in the same testis. We determined that Jun N-terminal kinase (JNK) activity is autonomously required for bam-lineage dedifferentiation. Overall, we show that dedifferentiation provides a mechanism to maintain the germline and ensure fertility under chronically stressful conditions.

scholarly journals Cell biology of stem cells: an enigma of asymmetry and self-renewal

2008 ◽  
Vol 180 (2) ◽  
pp. 257-260 ◽  
Author(s):  
Haifan Lin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Cell Cycle Regulators ◽  
Germline Stem Cells ◽  
Central Question ◽  
Daughter Cells ◽  
Mammalian Skin ◽  
Asymmetric Divisions ◽  
Stem Cell Division

Stem cells present a vast, new terrain of cell biology. A central question in stem cell research is how stem cells achieve asymmetric divisions to replicate themselves while producing differentiated daughter cells. This hallmark of stem cells is manifested either strictly during each mitosis or loosely among several divisions. Current research has revealed the crucial roles of niche signaling, intrinsic cell polarity, subcellular localization mechanism, asymmetric centrosomes and spindles, as well as cell cycle regulators in establishing self-renewing asymmetry during stem cell division. Much of this progress has benefited from studies in model stem cell systems such as Drosophila melanogaster neuroblasts and germline stem cells and mammalian skin stem cells. Further investigations of these questions in diverse types of stem cells will significantly advance our knowledge of cell biology and allow us to effectively harness stem cells for therapeutic applications.

scholarly journals Effects of shikonin on the development of ovarian follicles and female germline stem cells

2021 ◽  
Vol 49 (7) ◽  
pp. 030006052110294
Author(s):  
Shu-Xin Ma ◽  
Li-Bo Tang ◽  
Zhi-Hang Chen ◽  
Min-Li Wei ◽  
Zi-Juan Tang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ovarian Follicles ◽  
Germline Stem Cell ◽  
Stem Cell Markers ◽  
Germline Stem Cells ◽  
Primordial Follicles ◽  
Cell Markers ◽  
Female Germline ◽  
Ovarian Index

Objective To investigate the effects and potential mechanism of action of shikonin (SHK) on the development of ovarian follicles and female germline stem cells (FGSCs). Methods Female Kunming adult mice were administered SHK (0, 20 and 50 mg/kg) by oral gavage. Cultures of FGSCs were treated with SHK 32 μmol/l for 24 h. The ovarian index in mouse ovaries was calculated. Numbers of primordial, primary and atretic follicles were counted. Germline stem cell markers and apoptosis were examined. Levels of glutathione (GSH), superoxide dismutase (SOD) and reactive oxygen species (ROS) were measured. Results Both doses of SHK significantly decreased the ovarian index, the numbers of primordial follicles, primary follicles and antral follicles in mice. SHK significantly increased the numbers of atretic follicles and atretic corpora lutea. SHK promoted apoptosis in vivo and in vitro. SHK significantly decreased the levels of the germline stem cell markers. SHK significantly lowered GSH levels and the activity of SOD in the peripheral blood from mice, whereas SHK significantly elevated cellular ROS content in FGSCs. Conclusions These current results suggested that follicular development and FGSCs were suppressed by SHK through the induction of apoptosis and oxidative stress might be involved in this pathological process.

scholarly journals Aging germline stem cells in C. elegans

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 740-740
Author(s):  
E Jane Hubbard
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell System ◽  
Cell Aging ◽  
Germline Stem Cell ◽  
Germline Stem Cells ◽  
C Elegans ◽  
Cell Pool ◽  
Stem Cell System ◽  
Stem Cell Pool

Abstract Failure to maintain stem cells with age is associated with conditions such as tissue degeneration and increased susceptibility to tissue damage. We use the C. elegans germline stem cell system as a model to study stem cell aging. This system combines a well-established model for aging with an accessible stem cell system, providing a unique opportunity to understand how aging influences stem cell dynamics. The germline stem/progenitor pool in in C. elegans becomes depleted over time. At the cellular level, aging influences both the size of the stem cell pool and the proliferation rate of stem cells. The flux of differentiated cells also affects how aging impacts the pool. This depletion is partially alleviated in mutants with reduced insulin/IGF-like signaling via inhibition of the transcription factor DAF-16/FOXO. In this role, DAF-16 does not act in the germ line, and its anatomical requirements are different from its previously described roles in larval germline proliferation, dauer control, and lifespan regulation. We found that DAF-16/FOXO is required in certain somatic cells in the proximal part of the reproductive system to regulate the stem cell pool. We also find that the degree to which various age-defying perturbations affect lifespan does not correlate with their effect on germline stem cell maintenance. We are investigating additional aspects of aging germline stem cells using this system.

scholarly journals CentTracker: a trainable, machine learning-based tool for large-scale analyses of C. elegans germline stem cell mitosis

2020 ◽  
Author(s):  
M. Réda Zellag ◽  
Yifan Zhao ◽  
Vincent Poupart ◽  
Ramya Singh ◽  
Jean-Claude Labbé ◽  
...  
Keyword(s):  
Machine Learning ◽  
Stem Cells ◽  
Stem Cell ◽  
Large Scale ◽  
Spatial Clustering ◽  
Systematic Investigation ◽  
Germline Stem Cell ◽  
Analysis Tool ◽  
Germline Stem Cells

AbstractInvestigating the complex interactions between stem cells and their native environment requires an efficient means to image them in situ. Caenorhabditis elegans germline stem cells (GSCs) are distinctly accessible for intravital imaging; however, long-term image acquisition and analysis of dividing GSCs can be technically challenging. Here we present a systematic investigation into the technical factors impacting GSC physiology during live imaging and provide an optimized method for monitoring GSC mitosis under minimally disruptive conditions. We describe CentTracker, an automated and generalizable image analysis tool that uses machine learning to pair mitotic centrosomes and which can extract a variety of mitotic parameters rapidly from large-scale datasets. We employ CentTracker to assess a range of mitotic features in GSCs and show that subpopulations with distinct mitotic profiles are unlikely to exist within the stem cell pool. We further find evidence for spatial clustering of GSC mitoses within the germline tissue and for biases in mitotic spindle orientation relative to the germline’s distal-proximal axis, and thus the niche. The technical and analytical tools provided herein pave the way for large-scale screening studies of multiple mitotic processes in GSCs dividing in situ, in an intact tissue, in a living animal, under seemingly physiological conditions.

scholarly journals Aubergine and piRNAs repress the proto-oncogene Cbl for germline stem cell self-renewal

2017 ◽  
Author(s):  
Patricia Rojas-Ríos ◽  
Aymeric Chartier ◽  
Martine Simonelig
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mrna Translation ◽  
Translational Repression ◽  
Germline Stem Cell ◽  
Germline Stem Cells ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Cell Lineages

AbstractPIWI proteins have essential roles in germ cells and stem cell lineages. In Drosophila, Piwi is required in somatic niche cells and germline stem cells (GSCs) for GSC self-renewal and differentiation. Whether and how other PIWI proteins are involved in GSC biology remains unknown. Here, we show that Aubergine (Aub), another PIWI protein, is intrinsically required in GSCs for their self-renewal and differentiation. Aub loading with piRNAs is essential for these functions. The major role of Aub is in self-renewal and depends on mRNA regulation. We identify the Cbl proto-oncogene, a regulator of mammalian hematopoietic stem cells, as a novel GSC differentiation factor. Aub represses Cbl mRNA translation for GSC self-renewal, and does so through recruitment of the CCR4-NOT complex. This study reveals the role of piRNAs and PIWI proteins in translational repression for stem cell homeostasis and highlights piRNAs as major post-transcriptional regulators in key developmental decisions.

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