G-Protein signaling accelerates stem cell divisions in Drosophila males

AbstractAdult stem cells divide to renew the stem cell pool and replenish specialized cells that are lost due to death or usage. However, little is known about the mechanisms regulating how stem cells adjust to a demand for specialized cells. A failure of the stem cells to respond to this demand can have serious consequences, such as tissue loss, or prolonged recovery post injury.Here, we challenge the male germline stem cells (GSCs) of Drosophila melanogaster for the production of specialized cells using mating experiments. We show that repeated mating reduced the sperm pool and accelerated germline stem cell (GSC) divisions. The increase in GSC divisions depended on the activity of the highly conserved G-proteins. Germline expression of RNA-Interference (RNA-i) constructs against G-proteins or a dominant negative G-protein eliminated the increase in GSC divisions in mated males. Consistent with a role for the G-proteins in the regulation of GSC divisions, RNA-i against seven out of 35 G-protein coupled receptors (GPCRs) within the germline cells also eliminated the capability of males to accelerate their GSC divisions in response to mating. Our data show that GSCs are receptive to GPCR stimulus, potentially through a network of interactions among multiple signaling pathways.

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Symmetric Inheritance of Histones H3 in Drosophila Male Germline Stem Cell Divisions

10.1101/2021.10.22.465494 ◽

2021 ◽

Author(s):

Julie Ray ◽

Keith A. Maggert

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Germ Line ◽

Germline Stem Cell ◽

Cell Nuclei ◽

Cell Divisions ◽

Regulatory Information ◽

Alternative Hypotheses ◽

Stem Cell Divisions ◽

Gene Regulatory

Mitotically-stable epigenetic memory requires a mechanism for the maintenance of gene-regulatory information through the cell division cycle. Typically DNA-protein contacts are disrupted by DNA replication, but in some cases locus- specific association between DNA and overlying histones may appear to be maintained, providing a plausible mechanism for the transmission of histone-associated gene-regulatory information to daughter cells. Male Drosophila melanogaster testis germ stem cell divisions seem a clear example of such inheritance, as previously chromatin-bound histone H3.2 proteins (presumably with their post-translational modifications intact) have been reported to be retained in the germ stem cell nuclei, while newly synthesized histones are incorporated exclusively into daughter spermatogonial chromosomes. To investigate the rate of errors in this selective partitioning that may lead to defects in the epigenetic identity of germ stem cells, we employed a photoswitchable Dendra2 moiety as a C-terminal fusion on Histones H3; we could thereby discriminate histones translated before photoswitching and those translated after. We found instead that male germ line stem cell divisions show no evidence of asymmetric histone partitioning, even after a single division, and thus no evidence for locus-specific retention of either Histone H3.2 or Histone H3.3. We considered alternative hypotheses for the appearance of asymmetry and find that previous reports of asymmetric histone distribution in male germ stem cells can be satisfactorily explained by asynchrony between subsequent sister stem cell and spermatogonial divisions.

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Application of Nanomaterials in Regulating the Fate of Adipose-derived Stem Cells

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200502000343 ◽

2021 ◽

Vol 16 (1) ◽

pp. 3-13

Author(s):

Lang Wang ◽

Yong Li ◽

Maorui Zhang ◽

Kui Huang ◽

Shuanglin Peng ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Stem Cell Research ◽

Adult Stem Cells ◽

Adipose Derived Stem Cells ◽

Proliferation And Differentiation ◽

Recent Developments ◽

Good Biocompatibility ◽

Regulatory Effects ◽

New Treatment

Adipose-derived stem cells are adult stem cells which are easy to obtain and multi-potent. Stem-cell therapy has become a promising new treatment for many diseases, and plays an increasingly important role in the field of tissue repair, regeneration and reconstruction. The physicochemical properties of the extracellular microenvironment contribute to the regulation of the fate of stem cells. Nanomaterials have stable particle size, large specific surface area and good biocompatibility, which has led them being recognized as having broad application prospects in the field of biomedicine. In this paper, we review recent developments of nanomaterials in adipose-derived stem cell research. Taken together, the current literature indicates that nanomaterials can regulate the proliferation and differentiation of adipose-derived stem cells. However, the properties and regulatory effects of nanomaterials can vary widely depending on their composition. This review aims to provide a comprehensive guide for future stem-cell research on the use of nanomaterials.

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GSK3β, a Master Kinase in the Regulation of Adult Stem Cell Behavior

Cells ◽

10.3390/cells10020225 ◽

2021 ◽

Vol 10 (2) ◽

pp. 225

Author(s):

Claire Racaud-Sultan ◽

Nathalie Vergnolle

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Adult Stem Cells ◽

Glycogen Synthase ◽

Inflammatory Diseases ◽

Adult Stem Cell ◽

Leukemic Cells ◽

Cell Phenotype ◽

Epithelial Regeneration ◽

Cell Functions

In adult stem cells, Glycogen Synthase Kinase 3β (GSK3β) is at the crossroad of signaling pathways controlling survival, proliferation, adhesion and differentiation. The microenvironment plays a key role in the regulation of these cell functions and we have demonstrated that the GSK3β activity is strongly dependent on the engagement of integrins and protease-activated receptors (PARs). Downstream of the integrin α5β1 or PAR2 activation, a molecular complex is organized around the scaffolding proteins RACK1 and β-arrestin-2 respectively, containing the phosphatase PP2A responsible for GSK3β activation. As a consequence, a quiescent stem cell phenotype is established with high capacities to face apoptotic and metabolic stresses. A protective role of GSK3β has been found for hematopoietic and intestinal stem cells. Latters survived to de-adhesion through PAR2 activation, whereas formers were protected from cytotoxicity through α5β1 engagement. However, a prolonged activation of GSK3β promoted a defect in epithelial regeneration and a resistance to chemotherapy of leukemic cells, paving the way to chronic inflammatory diseases and to cancer resurgence, respectively. In both cases, a sexual dimorphism was measured in GSK3β-dependent cellular functions. GSK3β activity is a key marker for inflammatory and cancer diseases allowing adjusted therapy to sex, age and metabolic status of patients.

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Dielectrophoresis: A Review of Applications for Stem Cell Research

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/182581 ◽

2010 ◽

Vol 2010 ◽

pp. 1-7 ◽

Cited By ~ 85

Author(s):

Ronald Pethig ◽

Anoop Menachery ◽

Steve Pells ◽

Paul De Sousa

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Stem Cell Research ◽

Adult Stem Cells ◽

Surface Proteins ◽

Specific Cell ◽

State Changes ◽

Ultimate Fate ◽

Apoptosis And Necrosis ◽

Specific Cell Surface

Dielectrophoresis can discriminate distinct cellular identities in heterogeneous populations, and monitor cell state changes associated with activation and clonal expansion, apoptosis, and necrosis, without the need for biochemical labels. Demonstrated capabilities include the enrichment of haematopoetic stem cells from bone marrow and peripheral blood, and adult stem cells from adipose tissue. Recent research suggests that this technique can predict the ultimate fate of neural stem cells after differentiationbeforethe appearance of specific cell-surface proteins. This review summarises the properties of cells that contribute to their dielectrophoretic behaviour, and their relevance to stem cell research and translational applications.

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Quiescent, Slow-Cycling Stem Cell Populations in Cancer: A Review of the Evidence and Discussion of Significance

Journal of Oncology ◽

10.1155/2011/396076 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 159

Author(s):

Nathan Moore ◽

Stephen Lyle

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cells ◽

Adult Stem Cells ◽

Cell Populations ◽

Proliferative Potential ◽

Cell Cycle Regulators ◽

Slow Cycling ◽

Stem Cell Populations

Long-lived cancer stem cells (CSCs) with indefinite proliferative potential have been identified in multiple epithelial cancer types. These cells are likely derived from transformed adult stem cells and are thought to share many characteristics with their parental population, including a quiescent slow-cycling phenotype. Various label-retaining techniques have been used to identify normal slow cycling adult stem cell populations and offer a unique methodology to functionally identify and isolate cancer stem cells. The quiescent nature of CSCs represents an inherent mechanism that at least partially explains chemotherapy resistance and recurrence in posttherapy cancer patients. Isolating and understanding the cell cycle regulatory mechanisms of quiescent cancer cells will be a key component to creation of future therapies that better target CSCs and totally eradicate tumors. Here we review the evidence for quiescent CSC populations and explore potential cell cycle regulators that may serve as future targets for elimination of these cells.

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Article Commentary: Stem Cell Research in Cell Transplantation: An Analysis of Geopolitical Influence by Publications

Cell Transplantation ◽

10.3727/000000007783465190 ◽

2007 ◽

Vol 16 (8) ◽

pp. 867-873 ◽

Cited By ~ 5

Author(s):

David J. Eve ◽

Paul R. Sanberg

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Transplantation ◽

Adult Stem Cells ◽

Adult Stem Cell ◽

Therapeutic Area ◽

Fetal Stem Cells ◽

Major Player ◽

The Us ◽

Restricted Use

One of the fastest growing fields in researching treatments for neurodegenerative and other disorders is the use of stem cells. These cells are naturally occurring and can be obtained from three different stages of an organism's life: embryonic, fetal, and adult. In the US, political doctrine has restricted use of federal funds for stem cells, enhancing research towards an adult source. In order to determine how this legislation may be represented by the stem cell field, a retrospective analysis of stem cell articles published in the journal Cell Transplantation over a 2-year period was performed. Cell Transplantation is considered a translational journal from preclinical to clinical, so it was of interest to determine the publication outcome of stem cell articles 6 years after the US regulations. The distribution of the source of stem cells was found to be biased towards the adult stage, but relatively similar over the embryonic and fetal stages. The fetal stem cell reports were primarily neural in origin, whereas the adult stem cell ones were predominantly mesenchymal and used mainly in neural studies. The majority of stem cell studies published in Cell Transplantation were found to fall under the umbrella of neuroscience research. American scientists published the most articles using stem cells with a bias towards adult stem cells, supporting the effect of the legislation, whereas Europe was the leading continent with a bias towards embryonic and fetal stem cells, where research is “controlled” but not restricted. Japan was also a major player in the use of stem cells. Allogeneic transplants (where donor and recipient are the same species) were the most common transplants recorded, although the transplantation of human-derived stem cells into rodents was the most common specific transplantation performed. This demonstrates that the use of stem cells is an increasingly important field (with a doubling of papers between 2005 and 2006), which is likely to develop into a major therapeutic area over the next few decades and that funding restrictions can affect the type of research being performed.

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

eLife ◽

10.7554/elife.20977 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 14

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.

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Antioxidant Effects of Caffeic Acid Lead to Protection of Drosophila Intestinal Stem Cell Aging

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.735483 ◽

2021 ◽

Vol 9 ◽

Author(s):

Xiao Sheng ◽

Yuedan Zhu ◽

Juanyu Zhou ◽

La Yan ◽

Gang Du ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Caffeic Acid ◽

Stress Responses ◽

Adult Stem Cells ◽

Cell Function ◽

Cell Aging ◽

Positive Effects ◽

Age Related ◽

Tissue Aging

The dysfunction or exhaustion of adult stem cells during aging is closely linked to tissue aging and age-related diseases. Circumventing this aging-related exhaustion of adult stem cells could significantly alleviate the functional decline of organs. Therefore, identifying small molecular compounds that could prevent the age-related decline of stem cell function is a primary goal in anti-aging research. Caffeic acid (CA), a phenolic compound synthesized in plants, offers substantial health benefits for multiple age-related diseases and aging. However, the effects of CA on adult stem cells remain largely unknown. Using the Drosophila midgut as a model, this study showed that oral administration with CA significantly delayed age-associated Drosophila gut dysplasia caused by the dysregulation of intestinal stem cells (ISCs) upon aging. Moreover, administering CA retarded the decline of intestinal functions in aged Drosophila and prevented hyperproliferation of age-associated ISC by suppressing oxidative stress-associated JNK signaling. On the other hand, CA supplementation significantly ameliorated the gut hyperplasia defect and reduced environmentally induced mortality, revealing the positive effects of CA on tolerance to stress responses. Taken together, our findings report a crucial role of CA in delaying age-related changes in ISCs of Drosophila.

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