Stem cell niche organization in the Drosophila ovary requires the ECM component Perlecan

Díaz-Torres, Alfonsa; Rosales-Nieves, Alicia E.; Pearson, J. R. A.; Mateos, Carmen Santa-Cruz; Marín-Menguiano, Miriam; Marshall, Owen J.; Brand, Andrea H.; González-Reyes, Acaimo

doi:10.1016/j.cub.2021.01.071

Cited by 23 publications

(17 citation statements)

References 64 publications

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“…We assume that trol and type IV collagen work together to trap the Dpp protein on the basement membrane associated with CpCs, restricting the Dpp distribution within the GSC niche. During the course of the revision, Diaz‐Torres and colleagues published a paper showing the involvement of trol in the GSC niche function (Diaz‐Torres et al., 2021). They showed that trol is required for the proper formation of CpCs and for regulation of DE‐cadherin‐dependent anchoring of GSCs to CpCs.…”

Section: Discussionmentioning

confidence: 99%

Heparan sulfate proteoglycan molecules, syndecan and perlecan, have distinct roles in the maintenance of Drosophila germline stem cells

et al. 2021

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The Drosophila female germline stem cell (GSC) niche provides an excellent model for understanding the stem cell niche in vivo. The GSC niche is composed of stromal cells that provide growth factors for the maintenance of GSCs and the associated extracellular matrix (ECM). Although the function of stromal cells/growth factors has been well studied, the function of the ECM in the GSC niche is largely unknown. In this study, we investigated the function of syndecan and perlecan, molecules of the heparan sulfate proteoglycan (HSPG) family, as the main constituents of the ECM. We found that both of these genes were expressed in niche stromal cells, and knockdown of them in stromal cells decreased GSC number, indicating that these genes are important niche components. Interestingly, our genetic analysis revealed that the effects of syndecan and perlecan on the maintenance of GSC were distinct. While the knockdown of perlecan in the GSC niche increased the number of cystoblasts, a phenotype suggestive of delayed differentiation of GSCs, the same was not true in the context of syndecan. Notably, the overexpression of syndecan and perlecan did not cause an expansion of the GSC niche, opposing the results reported in the context of glypican, another HSPG gene. Altogether, our data suggest that HSPG genes contribute to the maintenance of GSCs through multiple mechanisms, such as the control of signal transduction, and ligand distribution/stabilization. Therefore, our study paves the way for a deeper understanding of the ECM functions in the stem cell niche.

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Section: Discussionmentioning

confidence: 99%

Heparan sulfate proteoglycan molecules, syndecan and perlecan, have distinct roles in the maintenance of Drosophila germline stem cells

et al. 2021

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“…The extracellular matrix (ECM) is an important remodeling component of ovarian niche, which is responsible for the cellular organization, cell-matrix adhesion and tissue stiffness (57). It is composed of Laminins, Perlecan, Collagen IV, Glutatin and mucin-type O-glycoproteins (58)(59), and the ECM composition is regulated by a family of proteolytic enzymes, matrix metalloproteinases (MMPs) (60). Tissue inhibitors of metalloproteinases (TIMPs) mediate the inhibition of MMP activity, which is accomplished by blocking the MMPs catalytic domain with the amino and carbonyl groups of the TIMP N-terminal cysteine residue (61).…”

Section: The Eggpl Mediates Gsc Differentiation Via the Mmp-dependent...mentioning

confidence: 99%

Single-cell RNA sequencing identifies regulators of differentiation and nutritional cues in Drosophila female germ cells

Sun

Nystul

Zhong

2022

Preprint

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Drosophila ovarian germline stem cells (GSCs) are powerful model for stem cell research. However, due to the scarcity of GSCs in ovarian tissue, it is difficult to obtain the transcriptional profile of GSCs and identify novel GSC markers. In this study, we took advantage of single cell RNA sequencing (scRNA-seq) to profile the germline cells and somatic cells in wild type Drosophila ovary. We then performed an in vivo RNAi screen and network analysis to identify genes that are involved in the early stages of germ cell differentiation. We identified 33 genes with limited expression during early germ cell development and identified 19 genes that potentially regulate germ cell differentiation. Among these, an uncharacterized gene, which we named eggplant (eggpl), is highly expressed in GSC and downregulated in early daughter cells. Upon RNAi knockdown of eggpl, we observed an increase in germ cell proliferation, an accumulation of cysts in the early mitotic (2- and 4-cell) stages and an increase in overall ovary size compared to control when flies were maintained on a standard diet. In flies fed a rich yeast diet, the expression of eggpl was significantly lower and the effects of eggpl RNAi were suppressed, suggesting that downregulation of eggpl may link nutritional status to germ cell proliferation and differentiation. We also found that the matrix metalloproteases, Mmp1 and Mmp2 as well as the tissue inhibitor of metalloproteases (Timp) are additional regulators of eggpl. Collectively, this study provides new insight into the signaling networks that regulate early germ cell development and identifies eggpl as a key player in this process.

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“…These niche cells provide GSCs with signals and physical support to prevent entry into differentiation ( Eliazer and Buszczak, 2011 ). The organisation of the ovarian niche is very well established and includes a specialised extracellular matrix, a terminal filament (TF) of 8-10 cells, a rosette of 6-8 CpCs connected to the TF via the ‘transition cell’ (TC) and 2-3 ECs placed in close contact with the CpCs ( Díaz-Torres et al, 2021 ; Panchal et al, 2017 ; Wang and Page-McCaw, 2018 ). This microenvironment orchestrates short-range signalling and provides physical space to maintain 2-4 GSCs per niche.…”

Section: Introductionmentioning

confidence: 99%

“…CpCs connected to the TF via the "transition cell" (TC) and 2-3 ECs placed in close contact with the CpCs (Díaz-Torres et al, 2021;Panchal et al, 2017;Wang and Page-McCaw, 2018).…”

Section: Introductionmentioning

confidence: 99%

Live imaging of the Drosophila ovarian niche shows spectrosome and centrosome dynamics during asymmetric germline stem cell division

et al. 2021

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Drosophila female germline stem cells (GSCs) are found inside the cellular niche at the tip of the ovary. They undergo asymmetric divisions to renew the stem cell lineage and to produce sibling cystoblasts that will in turn enter differentiation. GSCs and cystoblasts contain spectrosomes, membranous structures essential to orientate the mitotic spindle and that, particularly in GSCs, change shape depending on the cell cycle phase. Using live imaging and a GFP fusion of the spectrosome component Par-1, we follow the complete spectrosome cycle throughout GSC division and quantify the relative duration of the different spectrosome shapes. We also determine that the Par-1 kinase shuttles between the spectrosome and the cytoplasm during mitosis and observe the continuous addition of new material to the GSC and cystoblast spectrosomes. Next, we utilise the Fly-FUCCI tool to define in live and fixed tissues that GSCs have a shorter G1 compared to the G2 phase. The observation of centrosomes in dividing GSCs allowed us to determine that centrosomes separate very early in G1, prior to centriole duplication. Furthermore, we show that the anterior centrosome associates with the spectrosome only during mitosis and that, upon mitotic spindle assembly, it translocates to the cell cortex, where it remains anchored until centrosome separation. Finally, we demonstrate that the asymmetric division of GSCs is not an intrinsic property of these cells, since the spectrosome of GSC-like cells located outside of the niche can divide symmetrically. Thus, GSCs display unique properties during division, a behaviour influenced by the surrounding niche.

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Stem cell niche organization in the Drosophila ovary requires the ECM component Perlecan

Cited by 23 publications

References 64 publications

Heparan sulfate proteoglycan molecules, syndecan and perlecan, have distinct roles in the maintenance of Drosophila germline stem cells

Heparan sulfate proteoglycan molecules, syndecan and perlecan, have distinct roles in the maintenance of Drosophila germline stem cells

Single-cell RNA sequencing identifies regulators of differentiation and nutritional cues in Drosophila female germ cells

Live imaging of the Drosophila ovarian niche shows spectrosome and centrosome dynamics during asymmetric germline stem cell division

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