scholarly journals Alstrom syndrome gene is a stem-cell-specific regulator of centriole duplication in the Drosophila testis

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Cuie Chen ◽  
Yukiko M Yamashita
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Biological Significance ◽  
Germline Stem Cells ◽  
Centriole Duplication ◽  
Alström Syndrome ◽  
Male Germline ◽  
Stem Cell Divisions ◽  
Drosophila Testis ◽  
Alstrom Syndrome

Asymmetrically dividing stem cells often show asymmetric behavior of the mother versus daughter centrosomes, whereby the self-renewing stem cell selectively inherits the mother or daughter centrosome. Although the asymmetric centrosome behavior is widely conserved, its biological significance remains largely unclear. Here, we show that Alms1a, a Drosophila homolog of the human ciliopathy gene Alstrom syndrome, is enriched on the mother centrosome in Drosophila male germline stem cells (GSCs). Depletion of alms1a in GSCs, but not in differentiating germ cells, results in rapid loss of centrosomes due to a failure in daughter centriole duplication, suggesting that Alms1a has a stem-cell-specific function in centrosome duplication. Alms1a interacts with Sak/Plk4, a critical regulator of centriole duplication, more strongly at the GSC mother centrosome, further supporting Alms1a’s unique role in GSCs. Our results begin to reveal the unique regulation of stem cell centrosomes that may contribute to asymmetric stem cell divisions.

scholarly journals Discovery of Alstrom syndrome gene as a regulator of centrosome duplication in asymmetrically dividing stem cells in Drosophila.: Supplementary table-mass spectrometry

2018 ◽  
Author(s):  
Cuie Chen ◽  
Yukiko Yamashita
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Germline Stem Cells ◽  
Causative Gene ◽  
Centriole Duplication ◽  
Alström Syndrome ◽  
Mother And Daughter ◽  
Dividing Cells ◽  
Alstrom Syndrome ◽  
Daughter Centriole

Stereotypical inheritance of the mother vs. daughter centrosomes has been reported in several stem cells that divide asymmetrically. We report the identification of a protein that exhibits asymmetric localization between mother and daughter centrosomes in asymmetrically dividing Drosophila male germline stem cells (GSCs). We show that Alms1a, a Drosophila homolog of the causative gene for the human ciliopathy Alstrom Syndrome, is a ubiquitous mother centriole protein with a unique additional localization to the daughter centriole only in the mother centrosome of GSCs. Depletion of alms1a results in rapid loss of centrosomes due to failure in daughter centriole duplication. We reveal that alms1a is specifically required for centriole duplication in asymmetrically dividing cells but not in symmetrically dividing differentiating cells in multiple stem cell lineages. The unique requirement of alms1a in asymmetric dividing cells may shed light onto the molecular mechanisms of Alstrom syndrome pathogenesis.

scholarly journals Heparan sulfate regulates the number and centrosome positioning of Drosophila male germline stem cells

2016 ◽  
Vol 27 (6) ◽  
pp. 888-896 ◽  
Author(s):  
Daniel C. Levings ◽  
Takeshi Arashiro ◽  
Hiroshi Nakato
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Heparan Sulfate ◽  
Molecular Mechanisms ◽  
Asymmetric Division ◽  
Germline Stem Cells ◽  
Cell Behaviors ◽  
Male Germline ◽  
Drosophila Testis ◽  
Stem Cell Division

Stem cell division is tightly controlled via secreted signaling factors and cell adhesion molecules provided from local niche structures. Molecular mechanisms by which each niche component regulates stem cell behaviors remain to be elucidated. Here we show that heparan sulfate (HS), a class of glycosaminoglycan chains, regulates the number and asymmetric division of germline stem cells (GSCs) in the Drosophila testis. We found that GSC number is sensitive to the levels of 6- O sulfate groups on HS. Loss of 6- O sulfation also disrupted normal positioning of centrosomes, a process required for asymmetric division of GSCs. Blocking HS sulfation specifically in the niche, termed the hub, led to increased GSC numbers and mispositioning of centrosomes. The same treatment also perturbed the enrichment of Apc2, a component of the centrosome-anchoring machinery, at the hub–GSC interface. This perturbation of the centrosome-anchoring process ultimately led to an increase in the rate of spindle misorientation and symmetric GSC division. This study shows that specific HS modifications provide a novel regulatory mechanism for stem cell asymmetric division. The results also suggest that HS-mediated niche signaling acts upstream of GSC division orientation control.

scholarly journals Klp10A, a stem cell centrosome-enriched kinesin, balances asymmetries in Drosophila male germline stem cell division

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Cuie Chen ◽  
Mayu Inaba ◽  
Zsolt G Venkei ◽  
Yukiko M Yamashita
Keyword(s):  
Stem Cell ◽  
Cell Division ◽  
Cell Fate ◽  
Germline Stem Cell ◽  
Germline Stem Cells ◽  
Male Germline ◽  
Mother And Daughter ◽  
Stem Cell Divisions ◽  
Stem Cell Division ◽  
Male Germline Stem Cells

Asymmetric stem cell division is often accompanied by stereotypical inheritance of the mother and daughter centrosomes. However, it remains unknown whether and how stem cell centrosomes are uniquely regulated and how this regulation may contribute to stem cell fate. Here we identify Klp10A, a microtubule-depolymerizing kinesin of the kinesin-13 family, as the first protein enriched in the stem cell centrosome in Drosophila male germline stem cells (GSCs). Depletion of klp10A results in abnormal elongation of the mother centrosomes in GSCs, suggesting the existence of a stem cell-specific centrosome regulation program. Concomitant with mother centrosome elongation, GSCs form asymmetric spindle, wherein the elongated mother centrosome organizes considerably larger half spindle than the other. This leads to asymmetric cell size, yielding a smaller differentiating daughter cell. We propose that klp10A functions to counteract undesirable asymmetries that may result as a by-product of achieving asymmetries essential for successful stem cell divisions.

scholarly journals me31B regulates stem cell homeostasis by preventing excess dedifferentiation in the Drosophila male germline

2021 ◽  
Author(s):  
Lindy Jensen ◽  
Zsolt G. Venkei ◽  
George J. Watase ◽  
Bitarka Bisai ◽  
Scott Pletcher ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Critical Role ◽  
Stem Cell Population ◽  
Germline Stem Cells ◽  
Cell Identity ◽  
Stem Cell Maintenance ◽  
Differentiated Cells ◽  
Male Germline ◽  
Elevated Frequency

Tissue-specific stem cells maintain tissue homeostasis by providing a continuous supply of differentiated cells throughout the life of organisms. Differentiated/differentiating cells can revert back to a stem cell identity via dedifferentiation to help maintain the stem cell pool beyond the lifetime of individual stem cells. Although dedifferentiation is important to maintain the stem cell population, it is speculated to underlie tumorigenesis. Therefore, this process must be tightly controlled. Here we show that a translational regulator me31B plays a critical role in preventing excess dedifferentiation in the Drosophila male germline: in the absence of me31B, spermatogonia (SGs) dedifferentiate into germline stem cells (GSCs) at a dramatically elevated frequency. Our results show that the excess dedifferentiation is likely due to misregulation of nos, a key regulator of germ cell identity and GSC maintenance. Taken together, our data reveal negative regulation of dedifferentiation to balance stem cell maintenance with differentiation.

scholarly journals Centrosome misorientation mediates slowing of the cell cycle under limited nutrient conditions in Drosophila male germline stem cells

2012 ◽  
Vol 23 (8) ◽  
pp. 1524-1532 ◽  
Author(s):  
Therese M. Roth ◽  
C.-Y. Ason Chiang ◽  
Mayu Inaba ◽  
Hebao Yuan ◽  
Viktoria Salzmann ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Germline Stem Cells ◽  
Self Renewal ◽  
Stem Cell Regulation ◽  
Male Germline ◽  
Male Germline Stem Cells ◽  
Nutrient Conditions

Drosophila male germline stem cells (GSCs) divide asymmetrically, balancing self-renewal and differentiation. Although asymmetric stem cell division balances between self-renewal and differentiation, it does not dictate how frequently differentiating cells must be produced. In male GSCs, asymmetric GSC division is achieved by stereotyped positioning of the centrosome with respect to the stem cell niche. Recently we showed that the centrosome orientation checkpoint monitors the correct centrosome orientation to ensure an asymmetric outcome of the GSC division. When GSC centrosomes are not correctly oriented with respect to the niche, GSC cell cycle is arrested/delayed until the correct centrosome orientation is reacquired. Here we show that induction of centrosome misorientation upon culture in poor nutrient conditions mediates slowing of GSC cell proliferation via activation of the centrosome orientation checkpoint. Consistently, inactivation of the centrosome orientation checkpoint leads to lack of cell cycle slowdown even under poor nutrient conditions. We propose that centrosome misorientation serves as a mediator that transduces nutrient information into stem cell proliferation, providing a previously unappreciated mechanism of stem cell regulation in response to nutrient conditions.

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.

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