scholarly journals Cellular Functions of OCT-3/4 Regulated by Ubiquitination in Proliferating Cells

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 663
Author(s):  
Kwang-Hyun Baek ◽  
Jihye Choi ◽  
Chang-Zhu Pei
Keyword(s):  
Stem Cells ◽  
Cellular Proliferation ◽  
Critical Role ◽  
Embryonic Stem ◽  
Cell Types ◽  
Ubiquitin Proteasome System ◽  
Specific Cell ◽  
Cellular Mechanisms ◽  
Proliferating Cells ◽  
Proliferation And Differentiation

Octamer-binding transcription factor 3/4 (OCT-3/4), which is involved in the tumorigenesis of somatic cancers, has diverse functions during cancer development. Overexpression of OCT-3/4 has been detected in various human somatic tumors, indicating that OCT-3/4 activation may contribute to the development and progression of cancers. Stem cells can undergo self-renewal, pluripotency, and reprogramming with the help of at least four transcription factors, OCT-3/4, SRY box-containing gene 2 (SOX2), Krüppel-like factor 4 (KLF4), and c-MYC. Of these, OCT-3/4 plays a critical role in maintenance of undifferentiated state of embryonic stem cells (ESCs) and in production of induced pluripotent stem cells (iPSCs). Stem cells can undergo partitioning through mitosis and separate into specific cell types, three embryonic germ layers: the endoderm, the mesoderm, and the trophectoderm. It has been demonstrated that the stability of OCT-3/4 is mediated by the ubiquitin-proteasome system (UPS), which is one of the key cellular mechanisms for cellular homeostasis. The framework of the mechanism is simple, but the proteolytic machinery is complicated. Ubiquitination promotes protein degradation, and ubiquitination of OCT-3/4 leads to regulation of cellular proliferation and differentiation. Therefore, it is expected that OCT-3/4 may play a key role in proliferation and differentiation of proliferating cells.

scholarly journals The E3 Ligase Axotrophin/MARCH-7: Protein Expression Profiling of Human Tissues Reveals Links to Adult Stem Cells

2009 ◽  
Vol 58 (4) ◽  
pp. 301-308 ◽  
Author(s):  
Cristina A. Szigyarto ◽  
Paul Sibbons ◽  
Gill Williams ◽  
Mathias Uhlen ◽  
Su M. Metcalfe
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Protein Expression ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
Null Mouse ◽  
Specific Cell ◽  
Direct Role ◽  
Neuronal Progenitor

Axotrophin/MARCH-7 was first identified in mouse embryonic stem cells as a neural stem cell gene. Using the axotrophin/MARCH-7 null mouse, we discovered profound effects on T lymphocyte responses, including 8-fold hyperproliferation and 5-fold excess release of the stem cell cytokine leukemia inhibitory factor (LIF). Our further discovery that axotrophin/MARCH-7 is required for targeted degradation of the LIF receptor subunit gp190 implies a direct role in the regulation of LIF signaling. Bioinformatics studies revealed a highly conserved RING-CH domain in common with the MARCH family of E3-ubiquitin ligases, and accordingly, axotrophin was renamed “MARCH-7.” To probe protein expression of human axotrophin/MARCH-7, we prepared antibodies against different domains of the protein. Each antibody bound its specific target epitope with high affinity, and immunohistochemistry cross-validated target specificity. Forty-eight human tissue types were screened. Epithelial cells stained strongly, with trophoblasts having the greatest staining. In certain tissues, specific cell types were selectively positive, including neurons and neuronal progenitor cells in the hippocampus and cerebellum, endothelial sinusoids of the spleen, megakaryocytes in the bone marrow, crypt stem cells of the small intestine, and alveolar macrophages in the lung. Approximately 20% of central nervous system neuropils were positive. Notably, axotrophin/MARCH-7 has an expression profile that is distinct from that of other MARCH family members. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.

Cloning and stem cells

2010 ◽  
pp. 73-90
Author(s):  
Carlo Alberto Redi ◽  
Manuela Monti
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Ethical Issues ◽  
Embryonic Stem ◽  
Green Light ◽  
Transgenic Animals ◽  
Cell Types ◽  
Patient Specific ◽  
Specific Cell ◽  
Cord Injury

Cloning, the generation of genetically identical individuals, frequently occurs in plants and in several animal groups. Nowadays cloning is technically reproducible thanks to both embryo splitting and somatic cell nuclear transfer thus playing an important role in zootechnical applications (i.e., to increase transgenic animals for drug production) and in biomedicine (i.e, to produce embryonic stem cells in animal models, cybrids, etc.). The relevant historical advancements of these techniques and the related ethical issues are discussed. A brief review of the formation of a new individual as "a process" clearly leads to the impossibility for the biologist to unambiguously determine at which stage a new individual is first formed. However, the application of the scientific method to this issue produces a communal statement independent from ideological or religious opinion: ontogenetically, the material-energetic process originating and identifying a new individual is coincident with the moment in which the first genetically active copy of his genome is formed. Even the critical production of patient-specific stem cells (therapeutic cloning) it is most likely to be superseded and devoided of any ethical concerns thanks to the technical advancements developed by Shinia Yamanaka on the genetic reprogramming of terminally differentiated nuclei. The production of specific cell types might address the therapy of nearly all the pathologies. Noteworthy, starting April 2009 but actually beginning August 2010, the FDA gave green light to the first trial based on the administration of neuronal cells derived from human embryonic stem cells to 11 patients with severe spinal cord injury. Bio-political topics are briefly frameworked within the elaboration of ethical principles and laws that respect multiple values, which are necessary in multi-ethnic cultures.

The derivation and potential use of human embryonic stem cells

2001 ◽  
Vol 13 (8) ◽  
pp. 523 ◽  
Author(s):  
Alan O. Trounson
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Regenerative Medicine ◽  
Human Embryonic Stem Cells ◽  
High Efficiency ◽  
Es Cells ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Cell Types ◽  
Specific Cell

Human embryonic stem cells lines can be derived from human blastocysts at high efficiency (>50%) by immunosurgical isolation of the inner cell mass and culture on embryonic fibroblast cell lines. These cells will spontaneously differentiate into all the primary embryonic lineages in vitro and in vivo, but they are unable to form an integrated embryo or body plan by themselves or when combined with trophectoderm cells. They may be directed into a number of specific cell types and this enrichment process requires specific growth factors, cell-surface molecules, matrix molecules and secreted products of other cell types. Embryonic stem (ES) cells are immortal and represent a major potential for cell therapies for regenerative medicine. Their use in transplantation may depend on the formation of a large bank of suitable human leucocyte antigen (HLA) types or the genetic erasure of their HLA expression. Successful transplantation may also require induction of tolerance in recipients and ongoing immune suppression. Although it is possible to customize ES cells by therapeutic cloning or cytoplasmic transfer, it would appear unlikely that these strategies will be used extensively for producing ES cells compatible for transplantation. Embryonic stem cell research may deliver a new pathway for regenerative medicine.

Potential benefits of cell cloning for human medicine

1998 ◽  
Vol 10 (1) ◽  
pp. 121 ◽  
Author(s):  
A. Trounson ◽  
M. Pera
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Somatic Cell ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
Specific Cell ◽  
Somatic Cell Nucleus ◽  
Potential Benefits

The successful cloning of a mammal from an adult somatic cell nucleus opens new avenues for major advances in reproductive medicine, biotechnology and cellular-based transplantation therapies for degenerative diseases. At the same time, this breakthrough has generated much heated discussion concerning the ethics of cloning. Twinning is a form of cloning, and there are instances in clinical assisted reproduction in which the deliberate formation of twins by embryo dissection would seem ethically acceptable. Nuclear transfer technology might facilitate the derivation of human embryonic stem cells, capable of differentiation into a wide variety of somatic cell lineages. Directed differentiation of human embryonic stem cells into specific cell types in vitro could provide a universal source of cells for transplantation therapy. The potential benefits of therapeutics based on cloning technologies are considerable, and hasty legislation to ban all such procedures could block progress in critical arenas of biomedical research

scholarly journals Tumorőssejtek szerepe a melanoma progressziójában és heterogenitásában

2016 ◽  
Vol 157 (34) ◽  
pp. 1339-1348
Author(s):  
Balázs Széky ◽  
Pálma Silló ◽  
Melinda Fábián ◽  
Balázs Mayer ◽  
Sarolta Kárpáti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Asymmetric Cell Division ◽  
Critical Role ◽  
Embryonic Stem ◽  
Cell Types ◽  
Comprehensive Overview ◽  
Cell Clones ◽  
Cellular Markers ◽  
Cell Subpopulations

Over the past decade a rare cell population called cancer stem cells has been identified in both solid tumors and hematologic cancers. These cells are reminiscent of somatic and embryonic stem cells and play a critical role in the initiation and progression of malignancies. As all stem cells, they are able to undergo asymmetric cell division and hence renew themselves and create various other progenies with heterogenous phenotypes. A growing body of literature suggested that stem cell subpopulations contribute significantly to the growth and metastatic properties of melanoma. This review gives a comprehensive overview of the current literature on melanoma stem cells, with a special emphasis on the signaling pathways responsible for the homeostatic growth of melanocytes and the uncontrolled proliferation of melanoma cells. The importance of the local microenvironment are demonstrated through summarizing the role of various cell types, soluble factors and cell adhesion molecules in the progression of melanoma and the creation of treatment resistant cancer cell clones. Last but not least, the models of melanoma progression will be introduced and a variety of cellular markers will be presented that may be used to identify and therapeutically target melanoma. Orv. Hetil., 2016, 157(34), 1339–1348.

scholarly journals Genome-edited human stem cells expressing fluorescently labeled endocytic markers allow quantitative analysis of clathrin-mediated endocytosis during differentiation

2018 ◽  
Vol 217 (9) ◽  
pp. 3301-3311 ◽  
Author(s):  
Daphné Dambournet ◽  
Kem A. Sochacki ◽  
Aaron T. Cheng ◽  
Matthew Akamatsu ◽  
Justin W. Taraska ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem ◽  
Adaptor Protein ◽  
Cell Types ◽  
Specific Cell ◽  
Human Stem Cells ◽  
Cellular Processes ◽  
Neuronal Progenitor ◽  
Transmission Electron ◽  
Phosphoinositide 3 Kinase

We developed a general approach for investigation of how cellular processes become adapted for specific cell types during differentiation. Previous studies reported substantial differences in the morphology and dynamics of clathrin-mediated endocytosis (CME) sites. However, associating specific CME properties with distinct differentiated cell types and determining how these properties are developmentally specified during differentiation have been elusive. Using genome-edited human embryonic stem cells, and isogenic fibroblasts and neuronal progenitor cells derived from them, we established by live-cell imaging and platinum replica transmission electron microscopy that CME site dynamics and ultrastructure on the plasma membrane are precisely reprogrammed during differentiation. Expression levels for the endocytic adaptor protein AP2μ2 were found to underlie dramatic changes in CME dynamics and structure. Additionally, CME dependency on actin assembly and phosphoinositide-3 kinase activity are distinct for each cell type. Collectively, our results demonstrate that key CME properties are reprogrammed during differentiation at least in part through AP2μ2 expression regulation.

315 MELATONIN EFFECTS ON THE PROLIFERATION AND DIFFERENTIATION OF MOUSE EMBRYONIC STEM CELLS

2011 ◽  
Vol 23 (1) ◽  
pp. 254
Author(s):  
Y.-M. Yoo ◽  
E.-B. Jeung
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Zinc Finger ◽  
Cellular Proliferation ◽  
Ex Vivo ◽  
Es Cells ◽  
Embryonic Stem ◽  
Melatonin Treatment ◽  
Proliferation And Differentiation

Mouse embryonic stem (ES) cells constitute a versatile biological system that can facilitate major advances in the fields of cell and developmental biology. Several studies have been performed to determine whether melatonin can affect ex vivo and in vitro proliferation and differentiation of stem cells (mesenchymal and neural stem cells derived human, rats, and mice), but its effect on ES cells is largely unknown. Thus, we further examined in this study the effects of melatonin at biological or pharmacological concentrations (100 or 200 μM) on the proliferation and differentiation of ES cells (ES-E14TG2a cells) using an in vitro culture system (n = 3) by Western blot analysis and real-time PCR. We found that melatonin at 100 and 200 μM resulted in cellular proliferation and phosphorylation of ERK and Akt, respectively. Melatonin treatment also increased Bcl-2 expression and suppressed Bax gene expression and increased phosphorylation of GSK α/β. The transcription factor Oct-4, which contains the POU (N-terminal to homeobox) domain, and the transcription factor Sox2, the zinc finger transcription factor Zfp206, and the zinc finger gene REX-1 (Znf42), which contain the high mobility group domain, are all important for cellular pluripotency and preimplantation development. In this study, melatonin (100 μM) treatment induced Oct-4 and REX-1 expression at day 1 but not at days 2 and 3. In addition, Sox2 and Zfp206 expressions were not altered following melatonin treatment. Taken together, these results suggest that melatonin may affect Akt phosphorylation and stem cell proliferation at biological or pharmacological concentrations.

scholarly journals The Stem Cell Revolution Revealing Protozoan Parasites’ Secrets and Paving the Way towards Vaccine Development

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 105
Author(s):  
Alena Pance
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Vaccine Development ◽  
Embryonic Stem ◽  
Cell Types ◽  
Life Cycles ◽  
Host Cells ◽  
Neglected Diseases ◽  
Specific Cell ◽  
Protozoan Parasites

Protozoan infections are leading causes of morbidity and mortality in humans and some of the most important neglected diseases in the world. Despite relentless efforts devoted to vaccine and drug development, adequate tools to treat and prevent most of these diseases are still lacking. One of the greatest hurdles is the lack of understanding of host–parasite interactions. This gap in our knowledge comes from the fact that these parasites have complex life cycles, during which they infect a variety of specific cell types that are difficult to access or model in vitro. Even in those cases when host cells are readily available, these are generally terminally differentiated and difficult or impossible to manipulate genetically, which prevents assessing the role of human factors in these diseases. The advent of stem cell technology has opened exciting new possibilities to advance our knowledge in this field. The capacity to culture Embryonic Stem Cells, derive Induced Pluripotent Stem Cells from people and the development of protocols for differentiation into an ever-increasing variety of cell types and organoids, together with advances in genome editing, represent a huge resource to finally crack the mysteries protozoan parasites hold and unveil novel targets for prevention and treatment.

Revisiting the role of lysophosphatidic acid in stem cell biology

2021 ◽  
pp. 153537022110192
Author(s):  
Gábor Tigyi ◽  
Kuan-Hung Lin ◽  
Il Ho Jang ◽  
Sue Chin Lee
Keyword(s):  
Stem Cells ◽  
Lysophosphatidic Acid ◽  
Cell Biology ◽  
Embryonic Stem ◽  
Cell Types ◽  
Small Population ◽  
The Body ◽  
Specific Cell ◽  
Cancer Types ◽  
Regulatory Functions

Stem cells possess unique biological characteristics such as the ability to self-renew and to undergo multilineage differentiation into specialized cells. Whereas embryonic stem cells (ESC) can differentiate into all cell types of the body, somatic stem cells (SSC) are a population of stem cells located in distinct niches throughout the body that differentiate into the specific cell types of the tissue in which they reside in. SSC function mainly to restore cells as part of normal tissue homeostasis or to replenish cells that are damaged due to injury. Cancer stem-like cells (CSC) are said to be analogous to SSC in this manner where tumor growth and progression as well as metastasis are fueled by a small population of CSC that reside within the corresponding tumor. Moreover, emerging evidence indicates that CSC are inherently resistant to chemo- and radiotherapy that are often the cause of cancer relapse. Hence, major research efforts have been directed at identifying CSC populations in different cancer types and understanding their biology. Many factors are thought to regulate and maintain cell stemness, including bioactive lysophospholipids such as lysophosphatidic acid (LPA). In this review, we discuss some of the newly discovered functions of LPA not only in the regulation of CSC but also normal SSC, the similarities in these regulatory functions, and how these discoveries can pave way to the development of novel therapies in cancer and regenerative medicine.

Metabolic Regulation and Related Molecular Mechanisms in Various Stem Cell Functions

2020 ◽  
Vol 15 (6) ◽  
pp. 531-546 ◽  
Author(s):  
Hwa-Yong Lee ◽  
In-Sun Hong
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Oxidative Phosphorylation ◽  
Metabolic Pathways ◽  
Critical Role ◽  
The Self ◽  
Specific Cell ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Cell Functions

Recent studies on the mechanisms that link metabolic changes with stem cell fate have deepened our understanding of how specific metabolic pathways can regulate various stem cell functions during the development of an organism. Although it was originally thought to be merely a consequence of the specific cell state, metabolism is currently known to play a critical role in regulating the self-renewal capacity, differentiation potential, and quiescence of stem cells. Many studies in recent years have revealed that metabolic pathways regulate various stem cell behaviors (e.g., selfrenewal, migration, and differentiation) by modulating energy production through glycolysis or oxidative phosphorylation and by regulating the generation of metabolites, which can modulate multiple signaling pathways. Therefore, a more comprehensive understanding of stem cell metabolism could allow us to establish optimal culture conditions and differentiation methods that would increase stem cell expansion and function for cell-based therapies. However, little is known about how metabolic pathways regulate various stem cell functions. In this context, we review the current advances in metabolic research that have revealed functional roles for mitochondrial oxidative phosphorylation, anaerobic glycolysis, and oxidative stress during the self-renewal, differentiation and aging of various adult stem cell types. These approaches could provide novel strategies for the development of metabolic or pharmacological therapies to promote the regenerative potential of stem cells and subsequently promote their therapeutic utility.

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