scholarly journals Drosophila small ovary gene ensures germline stem cell maintenance and differentiation by silencing transposons and organising heterochromatin

2018 ◽  
Author(s):  
Ferenc Jankovics ◽  
Melinda Bence ◽  
Rita Sinka ◽  
Anikó Faragó ◽  
László Bodai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Genetic Interaction ◽  
Position Effect ◽  
Germline Stem Cell ◽  
Physical Interaction ◽  
Position Effect Variegation ◽  
Cell Nuclei ◽  
Transposon Silencing ◽  
Small Ovary

AbstractSelf-renewal and differentiation of stem cells is one of the fundamental biological phenomena relying on proper chromatin organisation. In our study, we describe a novel chromatin regulator encoded by the Drosophila small ovary (sov) gene. We demonstrate that sov is required in both the germline stem cells (GSCs) and the surrounding somatic niche cells to ensure GSC survival and differentiation. Sov maintains niche integrity and function by repressing transposon mobility, not only in the germline, but also in the soma. Protein interactome analysis of Sov revealed a physical interaction between Sov and HP1a. In the germ cell nuclei, Sov co-localises with HP1a, suggesting that Sov affects transposon repression as a component of the heterochromatin. In a position effect variegation assay, we found a dominant genetic interaction between sov and HP1a, indicating their functional cooperation in promoting the spread of heterochromatin. An in vivo tethering assay and FRAP analysis revealed that Sov enhances heterochromatin formation by supporting the recruitment of HP1a to the chromatin. We propose a model in which sov maintains GSC niche integrity by regulating piRNA-mediated transposon silencing as a heterochromatin regulator.Summary statementSmall ovary maintains the integrity of the stem cell niche by regulating piRNA-mediated transposon silencing acting as a key component of the heterochromatin.

scholarly journals Drosophila small ovary gene is required for transposon silencing and heterochromatin organization, and ensures germline stem cell maintenance and differentiation

Development ◽  
2018 ◽  
Vol 145 (23) ◽  
pp. dev170639 ◽  
Author(s):  
Ferenc Jankovics ◽  
Melinda Bence ◽  
Rita Sinka ◽  
Anikó Faragó ◽  
László Bodai ◽  
...  
Keyword(s):  
Stem Cell ◽  
Germline Stem Cell ◽  
Stem Cell Maintenance ◽  
Transposon Silencing ◽  
Small Ovary ◽  
Cell Maintenance

scholarly journals Symmetric Inheritance of Histones H3 in Drosophila Male Germline Stem Cell Divisions

2021 ◽  
Author(s):  
Julie Ray ◽  
Keith A. Maggert
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Germ Line ◽  
Germline Stem Cell ◽  
Cell Nuclei ◽  
Cell Divisions ◽  
Regulatory Information ◽  
Alternative Hypotheses ◽  
Stem Cell Divisions ◽  
Gene Regulatory

Mitotically-stable epigenetic memory requires a mechanism for the maintenance of gene-regulatory information through the cell division cycle. Typically DNA-protein contacts are disrupted by DNA replication, but in some cases locus- specific association between DNA and overlying histones may appear to be maintained, providing a plausible mechanism for the transmission of histone-associated gene-regulatory information to daughter cells. Male Drosophila melanogaster testis germ stem cell divisions seem a clear example of such inheritance, as previously chromatin-bound histone H3.2 proteins (presumably with their post-translational modifications intact) have been reported to be retained in the germ stem cell nuclei, while newly synthesized histones are incorporated exclusively into daughter spermatogonial chromosomes. To investigate the rate of errors in this selective partitioning that may lead to defects in the epigenetic identity of germ stem cells, we employed a photoswitchable Dendra2 moiety as a C-terminal fusion on Histones H3; we could thereby discriminate histones translated before photoswitching and those translated after. We found instead that male germ line stem cell divisions show no evidence of asymmetric histone partitioning, even after a single division, and thus no evidence for locus-specific retention of either Histone H3.2 or Histone H3.3. We considered alternative hypotheses for the appearance of asymmetry and find that previous reports of asymmetric histone distribution in male germ stem cells can be satisfactorily explained by asynchrony between subsequent sister stem cell and spermatogonial divisions.

scholarly journals The lysophospholipase D enzyme Gdpd3 is required to maintain chronic myelogenous leukaemia stem cells

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kazuhito Naka ◽  
Ryosuke Ochiai ◽  
Eriko Matsubara ◽  
Chie Kondo ◽  
Kyung-Min Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Cycle Progression ◽  
Chronic Myelogenous Leukaemia ◽  
Cancer Recurrence ◽  
Myelogenous Leukaemia ◽  
Cell Nuclei ◽  
Hypomorphic Mutation ◽  
Lysophospholipase D

Abstract Although advanced lipidomics technology facilitates quantitation of intracellular lipid components, little is known about the regulation of lipid metabolism in cancer cells. Here, we show that disruption of the Gdpd3 gene encoding a lysophospholipase D enzyme significantly decreased self-renewal capacity in murine chronic myelogenous leukaemia (CML) stem cells in vivo. Sophisticated lipidomics analyses revealed that Gdpd3 deficiency reduced levels of certain lysophosphatidic acids (LPAs) and lipid mediators in CML cells. Loss of Gdpd3 also activated AKT/mTORC1 signalling and cell cycle progression while suppressing Foxo3a/β-catenin interaction within CML stem cell nuclei. Strikingly, CML stem cells carrying a hypomorphic mutation of Lgr4/Gpr48, which encodes a leucine-rich repeat (LRR)-containing G-protein coupled receptor (GPCR) acting downstream of Gdpd3, displayed inadequate disease-initiating capacity in vivo. Our data showing that lysophospholipid metabolism is required for CML stem cell maintenance in vivo establish a new, biologically significant mechanism of cancer recurrence that is independent of oncogene addiction.

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 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 The Germline Stem Cell Niche Unit in Mammalian Testes

2012 ◽  
Vol 92 (2) ◽  
pp. 577-595 ◽  
Author(s):  
Jon M. Oatley ◽  
Ralph L. Brinster
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Stem Cell Niche ◽  
Germline Stem Cell ◽  
Tissue Specific ◽  
Support Cell ◽  
Age Related ◽  
Cell Niche ◽  
Germline Stem Cell Niche

This review addresses current understanding of the germline stem cell niche unit in mammalian testes. Spermatogenesis is a classic model of tissue-specific stem cell function relying on self-renewal and differentiation of spermatogonial stem cells (SSCs). These fate decisions are influenced by a niche microenvironment composed of a growth factor milieu that is provided by several testis somatic support cell populations. Investigations over the last two decades have identified key determinants of the SSC niche including cytokines that regulate SSC functions and support cells providing these factors, adhesion molecules that influence SSC homing, and developmental heterogeneity of the niche during postnatal aging. Emerging evidence suggests that Sertoli cells are a key support cell population influencing the formation and function of niches by secreting soluble factors and possibly orchestrating contributions of other support cells. Investigations with mice have shown that niche influence on SSC proliferation differs during early postnatal development and adulthood. Moreover, there is mounting evidence of an age-related decline in niche function, which is likely influenced by systemic factors. Defining the attributes of stem cell niches is key to developing methods to utilize these cells for regenerative medicine. The SSC population and associated niche comprise a valuable model system for study that provides fundamental knowledge about the biology of tissue-specific stem cells and their capacity to sustain homeostasis of regenerating tissue lineages. While the stem cell is essential for maintenance of all self-renewing tissues and has received considerable attention, the role of niche cells is at least as important and may prove to be more receptive to modification in regenerative medicine.

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 Stem Cells, Diet, and Physiology

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 740-740
Author(s):  
Daniela Drummond-Barbosa
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Lineage ◽  
Germline Stem Cell ◽  
Stem Cell Regulation ◽  
Stem Cell Lineage ◽  
Sensor Control ◽  
Nutrient Signaling ◽  
Multicellular Organisms

Abstract Nutrient availability, stresses, and aging affect tissue stem cells in multicellular organisms; yet, the underlying physiological mechanisms in vivo remains largely unexplored. Dr. Drummond-Barbosa pioneered using Drosophila to study the physiology of tissue stem cell regulation. Her laboratory played a major role in delineating how diet, brain insulin-like peptides, and the TOR nutrient sensor control the germline stem cell (GSC) lineage. They also discovered that adipocyte-specific disruption of amino acid transport, other nutrient signaling, and metabolic pathways causes distinct germline phenotypes. They also showed that nuclear receptors act in multiple tissues to affect the GSC lineage through direct and indirect mechanisms. More recently, her group has been exploring how other physiological stresses affect the GSC lineage. Her group’s studies point to extensive communication between the brain, adipocytes, hepatocyte-like cells, and the germline, and underscore the complexity of the physiological network that modulates stem cell lineage behavior.

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