scholarly journals The number of Follicle Stem Cells in a Drosophila ovariole.

2021 ◽  
Author(s):  
Daniel Kalderon ◽  
David Melamed ◽  
Amy Reilein
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Central Issue ◽  
Cell Lineages ◽  
General Relevance ◽  
Follicle Stem Cells ◽  
Drosophila Ovary ◽  
Lineage Analysis

A paper by Reilein et al (2017) presented several fundamental new insights into the behavior of adult Follicle Stem Cells (FSCs) in the Drosophila ovary, including evidence that each ovariole hosts a large number of FSCs (14-16) maintained by population asymmetry (Reilein et al., 2017), rather than just two FSCs, dividing with largely individually asymmetric outcomes, as originally proposed (Margolis and Spradling, 1995; Nystul and Spradling, 2007). Fadiga and Nystul (2019) contest some of these conclusions on the basis of their repetition of a multicolor lineage strategy used by Reilein et al (2017) and repetition of earlier single-color lineage analysis. Here we outline a number of shortcomings in the execution and interpretation of those experiments that, in our opinion, undermine their conclusions. The central issue of general relevance concerns the importance of comprehensively analyzing all stem cell lineages, independent of any pre-conceptions, in order to identify all constituents and capture heterogeneous behaviors.

scholarly journals Integrins control the positioning and proliferation of follicle stem cells in the Drosophila ovary

2008 ◽  
Vol 182 (4) ◽  
pp. 801-815 ◽  
Author(s):  
Alana M. O'Reilly ◽  
Hsiu-Hsiang Lee ◽  
Michael A. Simon
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Cell Communication ◽  
Self Renewal ◽  
Ovarian Stem Cells ◽  
Stem Cell Populations ◽  
Integrin Ligand ◽  
Follicle Stem Cells ◽  
Drosophila Ovary

Adult stem cells are maintained in specialized microenvironments called niches, which promote self-renewal and prevent differentiation. In this study, we show that follicle stem cells (FSCs) in the Drosophila melanogaster ovary rely on cues that are distinct from those of other ovarian stem cells to establish and maintain their unique niche. We demonstrate that integrins anchor FSCs to the basal lamina, enabling FSCs to maintain their characteristic morphology and position. Integrin-mediated FSC anchoring is also essential for proper development of differentiating prefollicle cells that arise from asymmetrical FSC divisions. Our results support a model in which FSCs contribute to the formation and maintenance of their own niche by producing the integrin ligand, laminin A (LanA). Together, LanA and integrins control FSC proliferation rates, a role that is separable from their function in FSC anchoring. Importantly, LanA-integrin function is not required to maintain other ovarian stem cell populations, demonstrating that distinct pathways regulate niche–stem cell communication within the same organ.

scholarly journals A Single-Cell Atlas and Lineage Analysis of the Adult Drosophila Ovary

2019 ◽  
Author(s):  
Katja Rust ◽  
Lauren Byrnes ◽  
Kevin Shengyang Yu ◽  
Jason S. Park ◽  
Julie B. Sneddon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Single Cell ◽  
Cell Types ◽  
Somatic Tissue ◽  
Lineage Tracing ◽  
Major Cell Type ◽  
Follicle Stem Cells ◽  
Drosophila Ovary ◽  
Adult Drosophila ◽  
Lineage Analysis

AbstractThe Drosophila ovary is a widely used model for germ cell and somatic tissue biology. We have used single-cell RNA-sequencing to build a comprehensive cell atlas of the adult Drosophila ovary containing unique transcriptional profiles for every major cell type in the ovary, including the germline and follicle stem cells. Using this atlas we identify novel tools for identification and manipulation of known and novel cell types and perform lineage tracing to test cellular relationships of previously unknown cell types. By this we discovered a new form of cellular plasticity in which inner germarial sheath cells convert to follicle stem cells in response to starvation.Graphical Abstract

scholarly journals EGFR signaling promotes self-renewal through the establishment of cell polarity in Drosophila follicle stem cells

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Angela Castanieto ◽  
Michael J Johnston ◽  
Todd G Nystul
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Polarity ◽  
Growth Factor Receptor ◽  
Egfr Signaling ◽  
Epithelial Stem Cells ◽  
Cell Fates ◽  
Liver Kinase B1 ◽  
Follicle Stem Cells ◽  
Drosophila Ovary

Epithelial stem cells divide asymmetrically, such that one daughter replenishes the stem cell pool and the other differentiates. We found that, in the epithelial follicle stem cell (FSC) lineage of the Drosophila ovary, epidermal growth factor receptor (EGFR) signaling functions specifically in the FSCs to promote the unique partially polarized state of the FSC, establish apical–basal polarity throughout the lineage, and promote FSC maintenance in the niche. In addition, we identified a novel connection between EGFR signaling and the cell-polarity regulator liver kinase B1 (LKB1), which indicates that EGFR signals through both the Ras–Raf–MEK–Erk pathway and through the LKB1–AMPK pathway to suppress apical identity. The development of apical–basal polarity is the earliest visible difference between FSCs and their daughters, and our findings demonstrate that the EGFR-mediated regulation of apical–basal polarity is essential for the segregation of stem cell and daughter cell fates.

scholarly journals Drosophila Boi limits Hedgehog levels to suppress follicle stem cell proliferation

2010 ◽  
Vol 191 (5) ◽  
pp. 943-952 ◽  
Author(s):  
Tiffiney R. Hartman ◽  
Daniel Zinshteyn ◽  
Heather K. Schofield ◽  
Emmanuelle Nicolas ◽  
Ami Okada ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Function ◽  
Apical Cell ◽  
Suppressive Effect ◽  
Stem Cell Proliferation ◽  
Apical Cells ◽  
And Function ◽  
Follicle Stem Cells ◽  
Drosophila Ovary

Stem cells depend on signals from cells within their microenvironment, or niche, as well as factors secreted by distant cells to regulate their maintenance and function. Here we show that Boi, a Hedgehog (Hh)-binding protein, is a novel suppressor of proliferation of follicle stem cells (FSCs) in the Drosophila ovary. Hh is expressed in apical cells, distant from the FSC niche, and diffuses to reach FSCs, where it promotes FSC proliferation. We show that Boi is expressed in apical cells and exerts its suppressive effect on FSC proliferation by binding to and sequestering Hh on the apical cell surface, thereby inhibiting Hh diffusion. Our studies demonstrate that cells distant from the local niche can regulate stem cell function through ligand sequestration, a mechanism that likely is conserved in other epithelial tissues.

scholarly journals Follicle Stem Cells (FSCs) in the Drosophila ovary; a critique of published studies defining the number, location and behavior of FSCs

2020 ◽  
Author(s):  
Daniel Kalderon ◽  
David Melamed ◽  
Amy Reilein
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cell ◽  
Lineage Tracing ◽  
Overwhelming Evidence ◽  
And Behavior ◽  
Follicle Stem Cells ◽  
Drosophila Ovary

SummaryA paper by Reilein et al., (2017) presented several key new insights into the behavior of adult Follicle Stem Cells (FSCs) in the Drosophila ovary, including overwhelming evidence that each ovariole hosts a large number of FSCs (about 14-16) maintained by population asymmetry (Reilein et al., 2017), rather than just two FSCs, dividing with largely individually asymmetric outcomes, as originally proposed (Margolis and Spradling, 1995; Nystul and Spradling, 2007). Here we provide further discussion asserting the merits of the conclusions of Reilein et al., (2017) and the deficiencies in the contrary assertions recently presented by Fadiga and Nystul (Fadiga and Nystul, 2019). The principles that we discuss here, particularly with regard to lineage tracing and population asymmetry, are common to the investigation of most types of adult stem cell and should therefore be instructive and of interest to investigators studying any type of adult stem cell. The improved understanding of FSC numbers, location and behavior afforded by Reilein et al., (2017) and Reilein et al., (2018) can only provide a firm foundation for future progress once they are widely appreciated and seen to be resistant to challenge, as described in detail here.

scholarly journals Patterns of Cell Division and the Risk of Cancer

Genetics ◽  
2003 ◽  
Vol 163 (4) ◽  
pp. 1527-1532 ◽  
Author(s):  
Steven A Frank ◽  
Yoh Iwasa ◽  
Martin A Nowak
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Basal Layer ◽  
Mutation Rates ◽  
Tissue Architecture ◽  
Cell Lineages ◽  
Cell Mutation ◽  
Long Stem ◽  
Risk Of Cancer ◽  
Transit Cell

Abstract Epidermal and intestinal tissues divide throughout life to replace lost surface cells. These renewing tissues have long-lived basal stem cell lineages that divide many times, each division producing one stem cell and one transit cell. The transit cell divides a limited number of times, producing cells that move up from the basal layer and eventually slough off from the surface. If mutation rates are the same in stem and transit divisions, we show that minimal cancer risk is obtained by using the fewest possible stem divisions subject to the constraints imposed by the need to renew the tissue. In this case, stem cells are a necessary risk imposed by the constraints of tissue architecture. Cairns suggested that stem cells may have lower mutation rates than transit cells do. We develop a mathematical model to study the consequences of different stem and transit mutation rates. Our model shows that stem cell mutation rates two or three orders of magnitude less than transit mutation rates may favor relatively more stem divisions and fewer transit divisions, perhaps explaining how renewing tissues allocate cell divisions between long stem and short transit lineages.

scholarly journals Mitochondrial Dynamics in the Drosophila Ovary Regulates Germ Stem Cell Number, Cell Fate, and Female Fertility

2021 ◽  
Vol 8 ◽  
Author(s):  
Marcia Garcez ◽  
Joana Branco-Santos ◽  
Patricia C. Gracio ◽  
Catarina C. F. Homem
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Mitochondrial Dynamics ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Cell Number ◽  
Female Fertility ◽  
Mitochondrial Activity ◽  
Drosophila Ovary

The fate and proliferative capacity of stem cells have been shown to strongly depend on their metabolic state. Mitochondria are the powerhouses of the cell being responsible for energy production via oxidative phosphorylation (OxPhos) as well as for several other metabolic pathways. Mitochondrial activity strongly depends on their structural organization, with their size and shape being regulated by mitochondrial fusion and fission, a process known as mitochondrial dynamics. However, the significance of mitochondrial dynamics in the regulation of stem cell metabolism and fate remains elusive. Here, we characterize the role of mitochondria morphology in female germ stem cells (GSCs) and in their more differentiated lineage. Mitochondria are particularly important in the female GSC lineage. Not only do they provide these cells with their energy requirements to generate the oocyte but they are also the only mitochondria pool to be inherited by the offspring. We show that the undifferentiated GSCs predominantly have fissed mitochondria, whereas more differentiated germ cells have more fused mitochondria. By reducing the levels of mitochondrial dynamics regulators, we show that both fused and fissed mitochondria are required for the maintenance of a stable GSC pool. Surprisingly, we found that disrupting mitochondrial dynamics in the germline also strongly affects nurse cells morphology, impairing egg chamber development and female fertility. Interestingly, reducing the levels of key enzymes in the Tricarboxylic Acid Cycle (TCA), known to cause OxPhos reduction, also affects GSC number. This defect in GSC self-renewal capacity indicates that at least basal levels of TCA/OxPhos are required in GSCs. Our findings show that mitochondrial dynamics is essential for female GSC maintenance and female fertility, and that mitochondria fusion and fission events are dynamically regulated during GSC differentiation, possibly to modulate their metabolic profile.

scholarly journals Mechanotransductive Differentiation of Hair Follicle Stem Cells Derived from Aged Eyelid Skin into Corneal Endothelial-Like Cells

2021 ◽  
Author(s):  
Christian Olszewski ◽  
Jessika Maassen ◽  
Rebecca Guenther ◽  
Claudia Skazik-Voogt ◽  
Angela Gutermuth
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Hair Follicles ◽  
Adherent Cell ◽  
Promising Alternative ◽  
Eyelid Skin ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

AbstractCorneal endothelial insufficiency is one of the leading causes of blindness. The main contemporary treatment for corneal blindness is endothelial keratoplasty, which, however, is unsatisfactory as a medical therapy due to the lack of donor corneas and graft rejection. Therefore, autologous stem cell-based corneal endothelial tissue substitutes may be a promising alternative to conventional grafts in the future. To address the age of most patients suffering from corneal endothelial deficiencies, we investigated the presence and potential of hair-derived stem cells from older tissue donors. Our studies revealed the presence of pluripotency- and neural crest-associated markers in tissue sections from blepharoplasty patients aged 50 to 80 years. In vitro outgrowths from eyelid hair follicles on collagen-coated tissue culture plates revealed a weak decrease in stem-cell potency. In contrast, cells within the spheres that spontaneously formed from the adherent cell layer retained full stem-cell potency and could be differentiated into cells of the ecto- meso and endodermal lineages. Although these highly potent hair follicle derived stem cells (HFSC) were only very slightly expandable, they were able to recognize the biomimicry of the Descemet’s-like topography and differentiate into corneal endothelial-like cells. In conclusion, HFSCs derived from epidermal skin of eyelid biopsies are a promising cell source to provide autologous corneal endothelial replacement for any age group of patients. Graphical Abstract

scholarly journals Escape of hair follicle stem cells causes stem cell exhaustion during aging

Nature Aging ◽  
2021 ◽  
Vol 1 (10) ◽  
pp. 889-903
Author(s):  
Chi Zhang ◽  
Dongmei Wang ◽  
Jingjing Wang ◽  
Li Wang ◽  
Wenli Qiu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Cell Exhaustion ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

scholarly journals Embryonic attenuated Wnt/β-catenin signaling defines niche location and long-term stem cell fate in hair follicle

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Zijian Xu ◽  
Wenjie Wang ◽  
Kaiju Jiang ◽  
Zhou Yu ◽  
Huanwei Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Adult Stem Cells ◽  
Stem Cell Markers ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

Long-term adult stem cells sustain tissue regeneration throughout the lifetime of an organism. They were hypothesized to originate from embryonic progenitor cells that acquire long-term self-renewal ability and multipotency at the end of organogenesis. The process through which this is achieved often remains unclear. Here, we discovered that long-term hair follicle stem cells arise from embryonic progenitor cells occupying a niche location that is defined by attenuated Wnt/β-catenin signaling. Hair follicle initiation is marked by placode formation, which depends on the activation of Wnt/β-catenin signaling. Soon afterwards, a region with attenuated Wnt/β-catenin signaling emerges in the upper follicle. Embryonic progenitor cells residing in this region gain expression of adult stem cell markers and become definitive long-term hair follicle stem cells at the end of organogenesis. Attenuation of Wnt/β-catenin signaling is a prerequisite for hair follicle stem cell specification because it suppresses Sox9, which is required for stem cell formation.

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