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 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 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.

Phenotypic alteration of limbal niche–associated limbal epithelial stem cell deficiency by ultraviolet-B exposure–induced phototoxicity in mice

2013 ◽  
Vol 91 (3) ◽  
pp. 165-175 ◽  
Author(s):  
Prosun Das ◽  
Jacintha Archana Pereira ◽  
Malay Chaklader ◽  
Aditya Law ◽  
Ketaki Bagchi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Continuous Production ◽  
Growth Factor Receptor ◽  
Explant Culture ◽  
Ultraviolet B ◽  
Stem Cell Marker ◽  
Epithelial Stem Cells ◽  
Cd38 Expression ◽  
Limbal Stem Cell

Good vision requires a healthy cornea, and a healthy cornea needs healthy stem cells. Limbal epithelial stem cells (LESCs) are a traditional source of corneal epithelial cells and are recruited for the continuous production of epithelium without seizing throughout an animal's life, which maintains corneal transparency. Like the maintenance of other adult somatic stem cells, the maintenance of LESCs depends on the specific microenvironmental niche in which they reside. The purpose of this study was to determine the microenvironmental damage associated with LESCs fate due to ultraviolet (UV)-B exposure in a mouse model. Structural alteration and deregulation of the stem cell and its neighboring niche components were observed by using clinical, morphological, explant culture study, and flowcytometric analysis, which demonstrated that the limbal microenvironment plays an important role in cornea-related disease development. In UV-exposed mice, overexpression of vascular endothelial growth factor receptor 2 indicated neovascularization, decreased CD38 expression signified the alteration of limbal epithelial superficial cells, and the loss of limbal stem cell marker p63 indicated limbal stem cell deficiency in the limbal vicinity. We concluded that LESC deficiency diseases (LESCDDs) are associated with pathophysiological changes in the LESC niche, with some inhibitory interception such as UV-B irradiation, which results in corneal defects.

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.

Pharmacological Inhibition of EGFR Signaling Enhances G-CSF Induced Hematopoietic Stem Cell Mobilization.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2337-2337
Author(s):  
Marnie A. Ryan ◽  
Ellen Xing ◽  
David Schleimer ◽  
Kalpana Nattamai ◽  
Deidre Daria ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Growth Factor Receptor ◽  
Stem Cell Mobilization ◽  
Egfr Signaling ◽  
Chromosome 11 ◽  
Hematopoietic Stem ◽  
Cell Mobilization

Abstract Mobilization of hematopoietic stem and progenitor cells (HSPCs) from bone marrow into peripheral blood by the cytokine G-CSF has become the preferred source of HSPCs for clinical stem cell transplants. However, up to 10% of donors fail to mobilize sufficient numbers of stem cells impeding autologous transplants or significantly delaying transplant recovery time. Consequently, novel regimens are warranted to increase the number of stem cells in peripheral blood upon mobilization. Using a forward genetic approach in the mouse, we map the epidermal growth factor receptor (EGFR) to a genetic region on murine chromosome 11 modifying G-CSF-mediated HSPC mobilization. Expression levels of EGFR in HSPCs were inversely correlated with HSPC mobilization, implying a negative role for EGFR signaling in mobilization. Genetic reduction of EGFR activity (waved2 mice) or treatment with the EGFR inhibitor erlotinib increased stem cell mobilization up to 5-fold in combination with G-CSF. Increased mobilization due do alteration of EGFR activity correlated with reduced activity of Cdc42 and consequently, inhibition of Cdc42 activity in vivo by a specific Cdc42 inhibitor similarly enhanced mobilization. Our findings reveal a novel signaling pathway regulating stem cell mobilization and thus provide new rationale for targeted pharmacological approaches to further improve HSPC mobilization and thus transplantation outcomes.

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 Stem Cells in the Path of Light, from Corneal to Retinal Reconstruction

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 873
Author(s):  
Ovidiu Samoila ◽  
Lacramioara Samoila
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Clinical Success ◽  
Corneal Stroma ◽  
Cell Transplant ◽  
Inclusion Criteria ◽  
Epithelial Stem Cells ◽  
Corneal Epithelial ◽  
Stem Cells Transplantation ◽  
Limbal Epithelial Stem Cells

The future of eye reconstruction invariably includes stem cells transplantation. Corneal limbus, corneal stroma, trabeculum, retinal cells, optic nerve, and all structures that are irreversibly damaged and have no means to be repaired or replaced, through conventional treatment or surgery, represent targets for stem cell reconstruction. This review tries to answer the question if there is any clinical validation for stem therapies, so far, starting from the cornea and, on the path of light, arriving to the retina. The investigation covers the last 10 years of publications. From 2385 published sources, we found 56 clinical studies matching inclusion criteria, 39 involving cornea, and 17 involving retina. So far, corneal epithelial reconstruction seems well validated clinically. Enough clinical data are collected to allow some form of standardization for the stem cell transplant procedures. Cultivated limbal epithelial stem cells (CLET), simple limbal epithelial transplant (SLET), and oral mucosa transplantation are implemented worldwide. In comparison, far less patients are investigated in retinal stem reconstructions, with lower anatomical and clinical success, so far. Intravitreal, subretinal, and suprachoroidal approach for retinal stem therapies face specific challenges.

scholarly journals Histone Acetyltransferases and Stem Cell Identity

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2407
Author(s):  
Ruicen He ◽  
Arthur Dantas ◽  
Karl Riabowol
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Epigenetic Modification ◽  
Cell Types ◽  
Histone Acetyltransferases ◽  
Specific Cell ◽  
Cell Fates ◽  
Cell Identity ◽  
Hematopoietic Stem

Acetylation of histones is a key epigenetic modification involved in transcriptional regulation. The addition of acetyl groups to histone tails generally reduces histone-DNA interactions in the nucleosome leading to increased accessibility for transcription factors and core transcriptional machinery to bind their target sequences. There are approximately 30 histone acetyltransferases and their corresponding complexes, each of which affect the expression of a subset of genes. Because cell identity is determined by gene expression profile, it is unsurprising that the HATs responsible for inducing expression of these genes play a crucial role in determining cell fate. Here, we explore the role of HATs in the maintenance and differentiation of various stem cell types. Several HAT complexes have been characterized to play an important role in activating genes that allow stem cells to self-renew. Knockdown or loss of their activity leads to reduced expression and or differentiation while particular HATs drive differentiation towards specific cell fates. In this study we review functions of the HAT complexes active in pluripotent stem cells, hematopoietic stem cells, muscle satellite cells, mesenchymal stem cells, neural stem cells, and cancer stem cells.

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