The germ line regulates somatic cyst cell proliferation and fate during Drosophila spermatogenesis

Development ◽  
1996 ◽  
Vol 122 (8) ◽  
pp. 2437-2447 ◽  
Author(s):  
P. Gonczy ◽  
S. DiNardo
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Cell Fate ◽  
Germ Cells ◽  
Germ Line ◽  
Lineage Tracing ◽  
Somatic Stem Cells ◽  
Daughter Cyst ◽  
Cyst Cell ◽  
Cyst Cells

Spermatogenesis relies on the function of germ-line stem cells, as a continuous supply of differentiated spermatids is produced throughout life. In Drosophila, there must also be somatic stem cells that produce the cyst cells that accompany germ cells throughout spermatogenesis. By lineage tracing, we demonstrate the existence of such somatic stem cells and confirm that of germ-line stem cells. The somatic stem cells likely correspond to the ultrastructurally described cyst progenitor cells. The stem cells for both the germ-line and cyst lineage are anchored around the hub of non-dividing somatic cells located at the testis tip. We then address whether germ cells regulate the behavior of somatic hub cells, cyst progenitors and their daughter cyst cells by analyzing cell proliferation and fate in testes in which the germ line has been genetically ablated. Daughter cyst cells, which normally withdraw from the cell cycle, continue to proliferate in the absence of germ cells. In addition, cells from the cyst lineage switch to the hub cell fate. Male-sterile alleles of chickadee and diaphanous, which are deficient in germ cells, exhibit similar cyst cell phenotypes. We conclude that signaling from germ cells regulates the proliferation and fate of cells in the somatic cyst lineage.

Germ cells of the mammalian female: A limited or renewable resource?

2021 ◽  
Author(s):  
Mathilde Hainaut ◽  
Hugh J Clarke
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Germ Cells ◽  
Germ Line ◽  
Marker Gene ◽  
Somatic Cells ◽  
Renewable Resource ◽  
Weight Of Evidence ◽  
Fetal Life

Abstract In many non-mammalian organisms, a population of germ-line stem cells supports continuing production of gametes during most or all the life of the individual, and germ-line stem cells are also present and functional in male mammals. Traditionally, however, they have been thought not to exist in female mammals, who instead generate all their germ cells during fetal life. Over the last several years, this dogma has been challenged by several reports, while supported by others. We describe and compare these conflicting studies with the aim of understanding how they came to opposing conclusions. We first consider studies that, by examining marker-gene expression, the fate of genetically marked cells, and consequences of depleting the oocyte population, addressed whether ovaries of post-natal females contain oogonial stem cells (OSC) that give rise to new oocytes. We next discuss whether ovaries contain cells that, even if inactive under physiological conditions, nonetheless possess OSC properties that can be revealed through cell-culture. We then examine studies of whether cells harvested after long-term culture of cells obtained from ovaries can, following transplantation into ovaries of recipient females, give rise to oocytes and offspring. Finally, we note studies where somatic cells have been re-programmed to acquire a female germ-cell fate. We conclude that the weight of evidence strongly supports the traditional interpretation that germ-line stem cells do not exist post-natally in female mammals. However, the ability to generate germ cells from somatic cells in vitro establishes a method to generate new gametes from cells of post-natal mammalian females.

scholarly journals Transcription factor AP2 controls cnidarian germ cell induction

Science ◽  
2020 ◽  
Vol 367 (6479) ◽  
pp. 757-762 ◽  
Author(s):  
Timothy Q. DuBuc ◽  
Christine E. Schnitzler ◽  
Eleni Chrysostomou ◽  
Emma T. McMahon ◽  
Febrimarsa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Germ Cell ◽  
Cell Fate ◽  
Germ Cells ◽  
Adult Stem Cells ◽  
Germ Line ◽  
Cell Induction ◽  
Cell Commitment ◽  
I Cells

Clonal animals do not sequester a germ line during embryogenesis. Instead, they have adult stem cells that contribute to somatic tissues or gametes. How germ fate is induced in these animals, and whether this process is related to bilaterian embryonic germline induction, is unknown. We show that transcription factor AP2 (Tfap2), a regulator of mammalian germ lines, acts to commit adult stem cells, known as i-cells, to the germ cell fate in the clonal cnidarian Hydractinia symbiolongicarpus. Tfap2 mutants lacked germ cells and gonads. Transplanted wild-type cells rescued gonad development but not germ cell induction in Tfap2 mutants. Forced expression of Tfap2 in i-cells converted them to germ cells. Therefore, Tfap2 is a regulator of germ cell commitment across germ line–sequestering and germ line–nonsequestering animals.

scholarly journals Vasa unveils a common origin of germ cells and of somatic stem cells from the posterior growth zone in the polychaete Platynereis dumerilii

2007 ◽  
Vol 306 (2) ◽  
pp. 599-611 ◽  
Author(s):  
N. Rebscher ◽  
F. Zelada-González ◽  
T.U. Banisch ◽  
F. Raible ◽  
D. Arendt
Keyword(s):  
Stem Cells ◽  
Germ Cells ◽  
Growth Zone ◽  
Common Origin ◽  
Somatic Stem Cells ◽  
Posterior Growth Zone ◽  
Platynereis Dumerilii

192 IDENTIFICATION AND CHARACTERIZATION OF Oct4-EGFP EXPRESSING CELLS IN TRANSGENIC PIG TESTIS

2014 ◽  
Vol 26 (1) ◽  
pp. 210
Author(s):  
M. Nowak-Imialek ◽  
N. Lachmann ◽  
D. Herrmann ◽  
F. Jacob ◽  
H. Niemann
Keyword(s):  
Stem Cells ◽  
Cell Population ◽  
Germ Cells ◽  
Germ Line ◽  
Cell Mass ◽  
Testicular Tissue ◽  
Egfp Expression ◽  
Cell Populations ◽  
Marker Genes ◽  
Transgenic Pigs

We have produced germ line transgenic pigs carrying the entire 18-kb genomic sequence of the murine Oct4 gene fused to the enhanced green fluorescent protein (EGFP) cDNA (OG2 construct; Nowak-Imialek et al., 2011 Stem Cells Dev.). Expression of the EGFP reporter construct is confined to germ line cells, the inner cell mass, and trophectoderm of blastocysts, and testicular germ cells, including putative spermatogonial stem cells (SSC). SSC are unique among stem cells because they can both self-renew and differentiate into spermatozoa. In-depth knowledge on porcine SSC has been hampered by the inability to isolate these cells from the complex cell population of the testis. In the Oct4-EGFP transgenic mouse, SSC are the only adult stem cells that express Oct4. Fluorescence microscopy of testicular tissue isolated from transgenic piglets revealed minimum numbers of EGFP-positive cells, whereas testicular tissue isolated from adult transgenic boars contained a high amount of EGFP fluorescent cells. Northern blot analysis confirmed stronger EGFP expression in the testis of adult transgenic pigs than in the testis from transgenic piglets. Time course and the signal intensity of EGFP expression in Oct4-EGFP testis paralleled mRNA expression of the endogenous Oct4 gene. Here, we used adult Oct4-EGFP transgenic pigs as a model for fluorescence-activated cell sorting (FACS)-based isolation of EGFP-expressing cells from testes. To obtain a single-cell suspension, the testes were enzymatically dissociated using two digestion steps. Thereafter, FACS based on EGFP expression was successfully used to purify specific testicular cell populations. Two cell populations, i.e. EGFP+ (14%) and EGFP– (45%) could be isolated. Subsequently, qualitative PCR analyses were performed on EGFP+, EGFP–, and unsorted cell populations using marker genes specific for pluripotency and undifferentiated germ cells (OCT4, FGFR3, UTF1, PGP9.5, GFRα1, CD90, SALL4), differentiating germ cells (c-KIT), meiosis (BOLL), spermatids (PRM2), and somatic cells (VIM, LHCGR). All of the genes, including OCT4, UTF1, FGFR3, PGP9.5, CD90, SALL4, and GFRα1 were expressed at least 3-fold and up to 12-fold greater in the EGFP-positive population. Vimentin, which is mainly expressed in Sertoli cells and LHCGR, which is mainly expressed in Leydig cells, were expressed in unsorted and EGFP– cell populations and at very low level in EGFP+ cells. Moreover, expression of the c-KIT and PRM2 markers were detected also in EGFP+ cell population, indicating that these cells contain also differentiating spermatogonia. To explore the characteristics of the Oct4-EGFP expressing cells in greater detail, localization in the porcine testis sections and analysis of co-expression with germ cell markers using immunohistochemistry is currently underway.

scholarly journals Proliferation and cell fate establishment during Arabidopsis male gametogenesis depends on the Retinoblastoma protein

2009 ◽  
Vol 106 (17) ◽  
pp. 7257-7262 ◽  
Author(s):  
Zhong Chen ◽  
Said Hafidh ◽  
Shi Hui Poh ◽  
David Twell ◽  
Frederic Berger
Keyword(s):  
Cell Proliferation ◽  
Germ Cell ◽  
Cell Fate ◽  
Vegetative Cell ◽  
Germ Line ◽  
Sperm Cells ◽  
Cyclin Dependent Kinase ◽  
Rb Protein ◽  
Male Gametogenesis ◽  
Male Germline

The Retinoblastoma (Rb) protein is a conserved repressor of cell proliferation. In animals and plants, deregulation of Rb protein causes hyperproliferation and perturbs cell differentiation to various degrees. However, the primary developmental impact of the loss of Rb protein has remained unclear. In this study we investigated the direct consequences of Rb protein knockout in the Arabidopsis male germline using cytological and molecular markers. The Arabidopsis germ line derives from the unequal division of the microspore, producing a small germ cell and a large terminally differentiated vegetative cell. A single division of the germ cell produces the 2 sperm cells. We observed that the loss of Rb protein does not have a major impact on microspore division but causes limited hyperproliferation of the vegetative cell and, to a lesser degree, of the sperm cells. In addition, cell fate is perturbed in a fraction of Rb-defective vegetative cells. These defects are rescued by preventing cell proliferation arising from down-regulation of cyclin-dependent kinase A1. Our results indicate that hyperproliferation caused by the loss of Rb protein prevents or delays cell determination during plant male gametogenesis, providing further evidence for a direct link between fate determination and cell proliferation.

Male germ line stem cells: from cell biology to cell therapy

2003 ◽  
Vol 15 (6) ◽  
pp. 323 ◽  
Author(s):  
David Pei-Cheng Lin ◽  
Ming-Yu Chang ◽  
Bo-Yie Chen ◽  
Han-Hsin Chang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Lines ◽  
Germ Cells ◽  
Germ Line ◽  
Current Status ◽  
Seminiferous Tubules ◽  
Male Germ Line ◽  
Male Germ Cells ◽  
Stem Cell Lines

Research using stem cells has several applications in basic biology and clinical medicine. Recent advances in the establishment of male germ line stem cells provided researchers with the ability to identify, isolate, maintain, expand and differentiate the spermatogonia, the primitive male germ cells, as cell lines under in vitro conditions. The ability to culture and manipulate stem cell lines from male germ cells has gradually facilitated research into spermatogenesis and male infertility, to an extent beyond that facilitated by the use of somatic stem cells. After the introduction of exogenous genes, the spermatogonial cells can be transplanted into the seminiferous tubules of recipients, where the transplanted cells can contribute to the offspring. The present review concentrates on the origin, life cycle and establishment of stem cell lines from male germ cells, as well as the current status of transplantation techniques and the application of spermatogonial stem cell lines.

scholarly journals Stem cells commit to differentiation following multiple induction events in the Drosophila testis.

2021 ◽  
Author(s):  
Marc Amoyel ◽  
Alice C Yuen ◽  
Kenzo-Hugo Hillion
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Germ Cells ◽  
Intercellular Communication ◽  
Self Renewal ◽  
Tor Pathway ◽  
Daughter Cells ◽  
Cyst Cells ◽  
Drosophila Testis ◽  
Primed State

How and when potential becomes restricted in differentiating stem cell daughters is poorly understood. While it is thought that signals from the niche are actively required to prevent differentiation, another model proposes that stem cells can reversibly transit between multiple states, some of which are primed, but not committed, to differentiate. In the Drosophila testis, somatic cyst stem cells (CySCs) generate cyst cells, which encapsulate the germline to support its development. We find that CySCs are maintained independently of niche self-renewal signals if activity of the PI3K/Tor pathway is inhibited. Conversely, PI3K/Tor is not sufficient alone to drive differentiation, suggesting that it acts to license cells for differentiation. Indeed, we find that the germline is required for differentiation of CySCs in response to PI3K/Tor elevation, indicating that final commitment to differentiation involves several steps and intercellular communication. We propose that CySC daughter cells are plastic, that their fate depends on the availability of neighbouring germ cells, and that PI3K/Tor acts to induce a primed state for CySC daughters to enable coordinated differentiation with 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 Differences and similarities between cancer and somatic stem cells: therapeutic implications

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Fiorella Rossi ◽  
Hunter Noren ◽  
Richard Jove ◽  
Vladimir Beljanski ◽  
Karl-Henrik Grinnemo
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Cancer Survival ◽  
Rapid Progression ◽  
Tumor Resistance ◽  
Somatic Stem Cells ◽  
Cancer Treatments ◽  
Tumor Mass ◽  
Therapeutic Implications ◽  
The Brain

AbstractOver the last decades, the cancer survival rate has increased due to personalized therapies, the discovery of targeted therapeutics and novel biological agents, and the application of palliative treatments. Despite these advances, tumor resistance to chemotherapy and radiation and rapid progression to metastatic disease are still seen in many patients. Evidence has shown that cancer stem cells (CSCs), a sub-population of cells that share many common characteristics with somatic stem cells (SSCs), contribute to this therapeutic failure. The most critical properties of CSCs are their self-renewal ability and their capacity for differentiation into heterogeneous populations of cancer cells. Although CSCs only constitute a low percentage of the total tumor mass, these cells can regrow the tumor mass on their own. Initially identified in leukemia, CSCs have subsequently been found in cancers of the breast, the colon, the pancreas, and the brain. Common genetic and phenotypic features found in both SSCs and CSCs, including upregulated signaling pathways such as Notch, Wnt, Hedgehog, and TGF-β. These pathways play fundamental roles in the development as well as in the control of cell survival and cell fate and are relevant to therapeutic targeting of CSCs. The differences in the expression of membrane proteins and exosome-delivered microRNAs between SSCs and CSCs are also important to specifically target the stem cells of the cancer. Further research efforts should be directed toward elucidation of the fundamental differences between SSCs and CSCs to improve existing therapies and generate new clinically relevant cancer treatments.

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