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 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 Cep120 is asymmetrically localized to the daughter centriole and is essential for centriole assembly

2010 ◽  
Vol 191 (2) ◽  
pp. 331-346 ◽  
Author(s):  
Moe R. Mahjoub ◽  
Zhigang Xie ◽  
Tim Stearns
Keyword(s):  
Basal Bodies ◽  
Animal Cells ◽  
Tracheal Epithelial Cells ◽  
Centriole Duplication ◽  
Photobleaching Recovery ◽  
Mother And Daughter ◽  
Tracheal Epithelial ◽  
Centriole Assembly ◽  
And Function ◽  
Daughter Centriole

Centrioles form the core of the centrosome in animal cells and function as basal bodies that nucleate and anchor cilia at the plasma membrane. In this paper, we report that Cep120 (Ccdc100), a protein previously shown to be involved in maintaining the neural progenitor pool in mouse brain, is associated with centriole structure and function. Cep120 is up-regulated sevenfold during differentiation of mouse tracheal epithelial cells (MTECs) and localizes to basal bodies. Cep120 localizes preferentially to the daughter centriole in cycling cells, and this asymmetry between mother and daughter centrioles is relieved coincident with new centriole assembly. Photobleaching recovery analysis identifies two pools of Cep120, differing in their halftime at the centriole. We find that Cep120 is required for centriole duplication in cycling cells, centriole amplification in MTECs, and centriole overduplication in S phase–arrested cells. We propose that Cep120 is required for centriole assembly and that the observed defect in neuronal migration might derive from a defect in this process.

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 Centrosome-dependent asymmetric inheritance of the midbody ring in Drosophila germline stem cell division

2014 ◽  
Vol 25 (2) ◽  
pp. 267-275 ◽  
Author(s):  
Viktoria Salzmann ◽  
Cuie Chen ◽  
C.-Y. Ason Chiang ◽  
Amita Tiyaboonchai ◽  
Michael Mayer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Germline Stem Cell ◽  
Dependent Manner ◽  
Germline Stem Cells ◽  
Cell Identity ◽  
Dividing Cells ◽  
Stem Cell Division ◽  
Functional Relevance

Many stem cells, including Drosophila germline stem cells (GSCs), divide asymmetrically, producing one stem cell and one differentiating daughter. Cytokinesis is often asymmetric, in that only one daughter cell inherits the midbody ring (MR) upon completion of abscission even in apparently symmetrically dividing cells. However, whether the asymmetry in cytokinesis correlates with cell fate or has functional relevance has been poorly explored. Here we show that the MR is asymmetrically segregated during GSC divisions in a centrosome age–dependent manner: male GSCs, which inherit the mother centrosome, exclude the MR, whereas female GSCs, which we here show inherit the daughter centrosome, inherit the MR. We further show that stem cell identity correlates with the mode of MR inheritance. Together our data suggest that the MR does not inherently dictate stem cell identity, although its stereotypical inheritance is under the control of stemness and potentially provides a platform for asymmetric segregation of certain factors.

Identification and behavior of epithelial stem cells in the Drosophila ovary

Development ◽  
1995 ◽  
Vol 121 (11) ◽  
pp. 3797-3807 ◽  
Author(s):  
J. Margolis ◽  
A. Spradling
Keyword(s):  
Stem Cells ◽  
Ovarian Follicle ◽  
Somatic Cells ◽  
Follicle Cells ◽  
Germline Stem Cells ◽  
Epithelial Stem Cells ◽  
Somatic Stem Cells ◽  
Young Females ◽  
Normal Site ◽  
Dividing Cells

Throughout their lives, adult Drosophila females continuously produce oocytes, each surrounded by an epithelial monolayer of follicle cells. To characterize the somatic stem cells that give rise to ovarian follicle cells, we marked dividing cells using FLP-catalyzed mitotic recombination and analyzed the resulting clones. Each ovariole in young females contains, on average, two somatic stem cells located near the border of germarium regions 2a and 2b. The somatic stem cells do not coordinate their divisions either with each other or with the germline stem cells. As females age, initially mosaic ovarioles become monoclonal, indicating that functional somatic stem cells have a finite life span. Analysis of agametic flies revealed that somatic cells continue to divide in the absence of a germline. Under these conditions, the somatic stem cells develop near the tip of the ovariole (the normal site of the germline stem cells), and a subpopulation of somatic cells that normally separates the germline and somatic stem cells is missing.

Centromere assembly and non-random sister chromatid segregation in stem cells

2020 ◽  
Vol 64 (2) ◽  
pp. 223-232 ◽  
Author(s):  
Ben L. Carty ◽  
Elaine M. Dunleavy
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Cell Fate ◽  
Sister Chromatid ◽  
Asymmetric Cell Division ◽  
Protein A ◽  
Germline Stem Cells ◽  
Sister Chromatids ◽  
Centromere Protein A ◽  
Oocyte Meiosis

Abstract Asymmetric cell division (ACD) produces daughter cells with separate distinct cell fates and is critical for the development and regulation of multicellular organisms. Epigenetic mechanisms are key players in cell fate determination. Centromeres, epigenetically specified loci defined by the presence of the histone H3-variant, centromere protein A (CENP-A), are essential for chromosome segregation at cell division. ACDs in stem cells and in oocyte meiosis have been proposed to be reliant on centromere integrity for the regulation of the non-random segregation of chromosomes. It has recently been shown that CENP-A is asymmetrically distributed between the centromeres of sister chromatids in male and female Drosophila germline stem cells (GSCs), with more CENP-A on sister chromatids to be segregated to the GSC. This imbalance in centromere strength correlates with the temporal and asymmetric assembly of the mitotic spindle and potentially orientates the cell to allow for biased sister chromatid retention in stem cells. In this essay, we discuss the recent evidence for asymmetric sister centromeres in stem cells. Thereafter, we discuss mechanistic avenues to establish this sister centromere asymmetry and how it ultimately might influence cell fate.

Liver fibrosis is common in Alstrom syndrome and can be identified using non-invasive tests

2014 ◽  
Author(s):  
Jonathan Hazlehurst ◽  
Matthew Armstrong ◽  
Jayne Hodgkiss ◽  
Rachel Crowley ◽  
Tarekegn Geberhiwot ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Non Invasive ◽  
Alström Syndrome ◽  
Alstrom Syndrome
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