scholarly journals The asymmetric segregation of damaged proteins is stem cell–type dependent

2013 ◽  
Vol 201 (4) ◽  
pp. 523-530 ◽  
Author(s):  
Mary Rose Bufalino ◽  
Brian DeVeale ◽  
Derek van der Kooy
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Intestinal Stem Cell ◽  
Germline Stem Cells ◽  
Cell Type ◽  
Chronological Life Span ◽  
A Cell ◽  
Female Germline

Asymmetric segregation of damaged proteins (DPs) during mitosis has been linked in yeast and bacteria to the protection of one cell from aging. Recent evidence suggests that stem cells may use a similar mechanism; however, to date there is no in vivo evidence demonstrating this effect in healthy adult stem cells. We report that stem cells in larval (neuroblast) and adult (female germline and intestinal stem cell) Drosophila melanogaster asymmetrically segregate DPs, such as proteins with the difficult-to-degrade and age-associated 2,4-hydroxynonenal (HNE) modification. Surprisingly, of the cells analyzed only the intestinal stem cell protects itself by segregating HNE to differentiating progeny, whereas the neuroblast and germline stem cells retain HNE during division. This led us to suggest that chronological life span, and not cell type, determines the amount of DPs a cell receives during division. Furthermore, we reveal a role for both niche-dependent and -independent mechanisms of asymmetric DP division.

STAT3 is required for proliferation and exhibits a cell type-specific binding preference in mouse female germline stem cells

2018 ◽  
Vol 14 (2) ◽  
pp. 95-102 ◽  
Author(s):  
Yunzhao Gu ◽  
Jun Wu ◽  
Wenxiao Yang ◽  
Chao Xia ◽  
Xinglong Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Specific Binding ◽  
Binding Pattern ◽  
Germline Stem Cells ◽  
Cell Type ◽  
Stat3 Signaling ◽  
Binding Preference ◽  
A Cell ◽  
Cell Type Specific ◽  
Female Germline

LIF-mediated STAT3 signaling contributes to proliferation and exhibits a cell-specific binding pattern in mouse female germline stem cells.

Accept or Reject: The Role of Immune Tolerance in the Development of Stem Cell Therapies and Possible Future Approaches

2020 ◽  
pp. 019262332091824
Author(s):  
Richard Haworth ◽  
Michaela Sharpe
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Embryonic Stem ◽  
Immune Recognition ◽  
Cell Of Origin ◽  
In Vivo Models ◽  
Cell Product ◽  
A Cell

In 2011, Goldring and colleagues published a review article describing the potential safety issues of novel stem cell-derived treatments. Immunogenicity and immunotoxicity of the administered cell product were considered risks in the light of clinical experience of transplantation. The relative immunogenicity of mesenchymal stem cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) was being addressed through in vitro and in vivo models. But the question arose as to whether the implanted cells needed to be identical to the recipient in every respect, including epigenetically, to evade immune recognition? If so, this set a high bar which may preclude use of many cells derived from iPSCs which have vestiges of a fetal phenotype and epigenetic memory of their cell of origin. However, for autologous iPSCs, the immunogenicity reduces once the surface antigen expression profile becomes close to that of the parent somatic cells. Therefore, a cell product containing incompletely differentiated cells could be more immunogenic. The properties of the administered cells, the immune privilege of the administration site, and the host immune status influence graft success or failure. In addition, the various approaches available to characterize potential immunogenicity of a cell therapy will be discussed.

scholarly journals Alternative polyadenylation of Pax3 controls muscle stem cell fate and muscle function

Science ◽  
2019 ◽  
Vol 366 (6466) ◽  
pp. 734-738 ◽  
Author(s):  
Antoine de Morree ◽  
Julian D. D. Klein ◽  
Qiang Gan ◽  
Jean Farup ◽  
Andoni Urtasun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Messenger Rna ◽  
Adult Stem Cells ◽  
Alternative Polyadenylation ◽  
Quiescent State ◽  
Stem Cell Fate ◽  
Activation Rate

Adult stem cells are essential for tissue homeostasis. In skeletal muscle, muscle stem cells (MuSCs) reside in a quiescent state, but little is known about the mechanisms that control homeostatic turnover. Here we show that, in mice, the variation in MuSC activation rate among different muscles (for example, limb versus diaphragm muscles) is determined by the levels of the transcription factor Pax3. We further show that Pax3 levels are controlled by alternative polyadenylation of its transcript, which is regulated by the small nucleolar RNA U1. Isoforms of the Pax3 messenger RNA that differ in their 3′ untranslated regions are differentially susceptible to regulation by microRNA miR206, which results in varying levels of the Pax3 protein in vivo. These findings highlight a previously unrecognized mechanism of the homeostatic regulation of stem cell fate by multiple RNA species.

scholarly journals Implications and Current Limitations of Oogenesis from Female Germline or Oogonial Stem Cells in Adult Mammalian Ovaries

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 93 ◽  
Author(s):  
Jessica Martin ◽  
Dori Woods ◽  
Jonathan Tilly
Keyword(s):  
Stem Cells ◽  
Adult Stem Cells ◽  
Ovarian Function ◽  
Mammalian Species ◽  
Large Body ◽  
The Body ◽  
Human Female ◽  
Female Germline

A now large body of evidence supports the existence of mitotically active germ cells in postnatal ovaries of diverse mammalian species, including humans. This opens the possibility that adult stem cells naturally committed to a germline fate could be leveraged for the production of female gametes outside of the body. The functional properties of these cells, referred to as female germline or oogonial stem cells (OSCs), in ovaries of women have recently been tested in various ways, including a very recent investigation of the differentiation capacity of human OSCs at a single cell level. The exciting insights gained from these experiments, coupled with other data derived from intraovarian transplantation and genetic tracing analyses in animal models that have established the capacity of OSCs to generate healthy eggs, embryos and offspring, should drive constructive discussions in this relatively new field to further exploring the value of these cells to the study, and potential management, of human female fertility. Here, we provide a brief history of the discovery and characterization of OSCs in mammals, as well as of the in-vivo significance of postnatal oogenesis to adult ovarian function. We then highlight several key observations made recently on the biology of OSCs, and integrate this information into a broader discussion of the potential value and limitations of these adult stem cells to achieving a greater understanding of human female gametogenesis in vivo and in vitro.

scholarly journals Enrichment of Female Germline Stem Cells from Mouse Ovaries Using the Differential Adhesion Method

2018 ◽  
Vol 46 (5) ◽  
pp. 2114-2126 ◽  
Author(s):  
Meng Wu ◽  
Jiaqiang Xiong ◽  
Lingwei Ma ◽  
Zhiyong Lu ◽  
Xian Qin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Akt Pathway ◽  
Germline Stem Cells ◽  
Self Renewal ◽  
Differential Adhesion ◽  
Proliferation And Differentiation ◽  
Phosphoinositide 3 Kinase ◽  
Female Germline

Background/Aims: The isolation and establishment of female germline stem cells (FGSCs) is controversial because of questions regarding the reliability and stability of the isolation method using antibody targeting mouse vasa homologue (MVH), and the molecular mechanism of FGSCs self-renewal remains unclear. Thus, there needs to be a simple and reliable method for sorting FGSCs to study them. Methods: We applied the differential adhesion method to enrich FGSCs (DA-FGSCs) from mouse ovaries. Through four rounds of purification and 7-9 subsequent passages, DA-FGSC lines were established. In addition, we assessed the role of the phosphoinositide-3 kinase (PI3K)-AKT pathway in regulating FGSC self-renewal. Results: The obtained DA-FGSCs spontaneously differentiated into oocyte-like cells in vitro and formed functional eggs in vivo that were fertilized and produced healthy offspring. AKT was rapidly phosphorylated when the proliferation rate of FGSCs increased after 10 passages, and the addition of a chemical PI3K inhibitor prevented FGSCs self-renewal. Furthermore, over-expression of AKT-induced proliferation and differentiation of FGSCs, c-Myc, Oct-4 and Gdf-9 levels were increased. Conclusions: The differential adhesion method provides a more feasible approach and is an easier procedure to establish FGSC lines than traditional methods. The AKT pathway plays an important role in regulation of the proliferation and maintenance of FGSCs. These findings could help promote stem cell studies and provide a better understanding of causes of ovarian infertility, thereby providing potential treatments for infertility.

scholarly journals Increased Understanding of Stem Cell Behavior in Neurodegenerative and Neuromuscular Disorders by Use of Noninvasive Cell Imaging

2016 ◽  
Vol 2016 ◽  
pp. 1-20 ◽  
Author(s):  
Bryan Holvoet ◽  
Liesbeth De Waele ◽  
Mattia Quattrocelli ◽  
Olivier Gheysens ◽  
Maurillio Sampaolesi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Imaging ◽  
Neuromuscular Disorders ◽  
Major Change ◽  
Full Potential ◽  
Cell Type ◽  
Beneficial Effects ◽  
Cell Monitoring

Numerous neurodegenerative and neuromuscular disorders are associated with cell-specific depletion in the human body. This imbalance in tissue homeostasis is in healthy individuals repaired by the presence of endogenous stem cells that can replace the lost cell type. However, in most disorders, a genetic origin or limited presence or exhaustion of stem cells impairs correct cell replacement. During the last 30 years, methods to readily isolate and expand stem cells have been developed and this resulted in a major change in the regenerative medicine field as it generates sufficient amount of cells for human transplantation applications. Furthermore, stem cells have been shown to release cytokines with beneficial effects for several diseases. At present however, clinical stem cell transplantations studies are struggling to demonstrate clinical efficacy despite promising preclinical results. Therefore, to allow stem cell therapy to achieve its full potential, more insight in theirin vivobehavior has to be achieved. Different methods to noninvasively monitor these cells have been developed and are discussed. In some cases, stem cell monitoring even reached the clinical setting. We anticipate that by further exploring these imaging possibilities and unraveling theirin vivobehavior further improvement in stem cell transplantations will be achieved.

scholarly journals Intestinal Stem Cell Niche Insights Gathered from Both In Vivo and Novel In Vitro Models

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Nikolce Gjorevski ◽  
Paloma Ordóñez-Morán
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Cell Function ◽  
Complex Structure ◽  
Intestinal Stem Cell ◽  
Intestinal Damage ◽  
Cell Niche

Intestinal stem cells are located at the base of the crypts and are surrounded by a complex structure called niche. This environment is composed mainly of epithelial cells and stroma which provides signals that govern cell maintenance, proliferation, and differentiation. Understanding how the niche regulates stem cell fate by controlling developmental signaling pathways will help us to define how stem cells choose between self-renewal and differentiation and how they maintain their undifferentiated state. Tractable in vitro assay systems, which reflect the complexity of the in vivo situation but provide higher level of control, would likely be crucial in identifying new players and mechanisms controlling stem cell function. Knowledge of the intestinal stem cell niche gathered from both in vivo and novel in vitro models may help us improve therapies for tumorigenesis and intestinal damage and make autologous intestinal transplants a feasible clinical practice.

scholarly journals Effects of shikonin on the development of ovarian follicles and female germline stem cells

2021 ◽  
Vol 49 (7) ◽  
pp. 030006052110294
Author(s):  
Shu-Xin Ma ◽  
Li-Bo Tang ◽  
Zhi-Hang Chen ◽  
Min-Li Wei ◽  
Zi-Juan Tang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ovarian Follicles ◽  
Germline Stem Cell ◽  
Stem Cell Markers ◽  
Germline Stem Cells ◽  
Primordial Follicles ◽  
Cell Markers ◽  
Female Germline ◽  
Ovarian Index

Objective To investigate the effects and potential mechanism of action of shikonin (SHK) on the development of ovarian follicles and female germline stem cells (FGSCs). Methods Female Kunming adult mice were administered SHK (0, 20 and 50 mg/kg) by oral gavage. Cultures of FGSCs were treated with SHK 32 μmol/l for 24 h. The ovarian index in mouse ovaries was calculated. Numbers of primordial, primary and atretic follicles were counted. Germline stem cell markers and apoptosis were examined. Levels of glutathione (GSH), superoxide dismutase (SOD) and reactive oxygen species (ROS) were measured. Results Both doses of SHK significantly decreased the ovarian index, the numbers of primordial follicles, primary follicles and antral follicles in mice. SHK significantly increased the numbers of atretic follicles and atretic corpora lutea. SHK promoted apoptosis in vivo and in vitro. SHK significantly decreased the levels of the germline stem cell markers. SHK significantly lowered GSH levels and the activity of SOD in the peripheral blood from mice, whereas SHK significantly elevated cellular ROS content in FGSCs. Conclusions These current results suggested that follicular development and FGSCs were suppressed by SHK through the induction of apoptosis and oxidative stress might be involved in this pathological process.

Defining Adult Stem Cells by Function, not by Phenotype

2018 ◽  
Vol 87 (1) ◽  
pp. 1015-1027 ◽  
Author(s):  
Hans Clevers ◽  
Fiona M. Watt
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Tissue Repair ◽  
Adult Stem Cells ◽  
Cell Function ◽  
Open Approach ◽  
Physical Entity ◽  
Hematopoietic Stem ◽  
A Cell

Central to the classical hematopoietic stem cell (HSC) paradigm is the concept that the maintenance of blood cell numbers is exclusively executed by a discrete physical entity: the transplantable HSC. The HSC paradigm has served as a stereotypic template in stem cell biology, yet the search for rare, hardwired professional stem cells has remained futile in most other tissues. In a more open approach, the focus on the search for stem cells as a physical entity may need to be replaced by the search for stem cell function, operationally defined as the ability of an organ to replace lost cells. The nature of such a cell may be different under steady state conditions and during tissue repair. We discuss emerging examples including the renewal strategies of the skin, gut epithelium, liver, lung, and mammary gland in comparison with those of the hematopoietic system. While certain key housekeeping and developmental signaling pathways are shared between different stem cell systems, there may be no general, deeper principles underlying the renewal mechanisms of the various individual tissues.

scholarly journals Offspring production of haploid spermatid-like cells derived from mouse female germline stem cells with chromatin condensation

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiaopeng Hu ◽  
Hu Wang ◽  
Geng. G. Tian ◽  
Changliang Hou ◽  
Bo Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Retinoic Acid ◽  
Y Chromosome ◽  
Germ Cells ◽  
Chromatin Condensation ◽  
Germline Stem Cells ◽  
Chromosome Conformation ◽  
Female Germline

Abstract Background During male meiosis, the Y chromosome can form perfect pairing with the X chromosome. However, it is unclear whether mammalian Female germline stem cells (FGSCs) without a Y chromosome can transdifferentiate into functional haploid spermatid-like cells (SLCs). Results We found that spermatogenesis was restarted by transplanting FGSCs into Kitw/wv mutant testes. Complete meiosis and formation of SLCs was induced in vitro by testicular cells of Kitw/wv mutant mice, cytokines and retinoic acid. Healthy offspring were produced by sperm and SLCs derived from the in vivo and in vitro transdifferentiation of FGSCs, respectively. Furthermore, high-throughput chromosome conformation capture sequencing(Hi-C-seq) and “bivalent” (H3K4me3-H3K27me3) micro chromatin immunoprecipitation sequencing (μChIP-seq) experiments showed that stimulated by retinoic acid gene 8 (STRA8)/protamine 1 (PRM1)-positive transdifferentiated germ cells (tGCs) and male germ cells (mGCs) display similar chromatin dynamics and chromatin condensation during in vitro spermatogenesis. Conclusion This study demonstrates that sperm can be produced from FGSCs without a Y chromosome. This suggests a strategy for dairy cattle breeding to produce only female offspring with a high-quality genetic background.

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