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.

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.

Derivation characteristics and perspectives for mammalian pluripotential stem cells

2005 ◽  
Vol 17 (2) ◽  
pp. 135 ◽  
Author(s):  
Alan Trounson
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Lines ◽  
Nuclear Transfer ◽  
Cell Mass ◽  
Embryonic Stem ◽  
The Body ◽  
Preimplantation Embryos ◽  
Specific Cell ◽  
Wide Range

Pluripotential stem cells have been derived in mice and primates from preimplantation embryos, postimplantation embryos and bone marrow stroma. Embryonic stem cells established from the inner cell mass of the mouse and human blastocyst can be maintained in an undifferentiated state for a long time by continuous passage on embryonic fibroblasts or in the presence of specific inhibitors of differentiation. Pluripotential stem cells can be induced to differentiate into all the tissues of the body and are able to colonise tissues of interest after transplantation. In mouse models of disease, there are numerous examples of improved tissue function and correction of pathological phenotype. Embryonic stem cells can be derived by nuclear transfer to establish genome-specific cell lines and, in mice, it has been shown that embryonic stem cells are more successfully reprogrammed for development by nuclear transfer than somatic cells. Pluripotential stem cells are a very valuable research resource for the analysis of differentiation pathways, functional genomics, tissue engineering and drug screening. Clinical applications may include both cell therapy and gene therapy for a wide range of tissue injury and degeneration. There is considerable interest in the development of pluripotential stem cell lines in many mammalian species for similar research interests and applications.

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.

scholarly journals Epigenetic Manipulation Facilitates the Generation of Skeletal Muscle Cells from Pluripotent Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Tomohiko Akiyama ◽  
Shunichi Wakabayashi ◽  
Atsumi Soma ◽  
Saeko Sato ◽  
Yuhki Nakatake ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Myogenic Differentiation ◽  
Ectopic Expression ◽  
Cell Types ◽  
Culture Conditions ◽  
The Body ◽  
Specific Cell ◽  
Modifying Factors

Human pluripotent stem cells (hPSCs) have the capacity to differentiate into essentially all cell types in the body. Such differentiation can be directed to specific cell types by appropriate cell culture conditions or overexpressing lineage-defining transcription factors (TFs). Especially, for the activation of myogenic program, early studies have shown the effectiveness of enforced expression of TFs associated with myogenic differentiation, such as PAX7 and MYOD1. However, the efficiency of direct differentiation was rather low, most likely due to chromatin features unique to hPSCs, which hinder the access of TFs to genes involved in muscle differentiation. Indeed, recent studies have demonstrated that ectopic expression of epigenetic-modifying factors such as a histone demethylase and an ATP-dependent remodeling factor significantly enhances myogenic differentiation from hPSCs. In this article, we review the recent progress for in vitro generation of skeletal muscles from hPSCs through forced epigenetic and transcriptional manipulation.

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.

1. What are stem cells?

2021 ◽  
pp. 1-18
Author(s):  
Jonathan Slack
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Structural Unit ◽  
Embryonic Stem ◽  
Cell Types ◽  
The Body ◽  
Differentiated Cells ◽  
Mammalian Embryos ◽  
A Cell

‘What are stem cells?’ explains that a stem cell is a cell that can both reproduce itself and generate offspring of different functional cell types and begins by considering the nature of cells in general, wherein cells are understood to be the ultimate structural unit of an animal or plant body. Stem cells in the body persist long term, usually for the lifetime of the organism. Good examples of differentiated cells arising from stem cells are those of the skin, the blood, and the lining of the intestine. Embryonic stem cells are grown in culture from early mammalian embryos. The reason that stem cell research is seen as the source for new cures is largely because this technology offers a route to cell therapy.

scholarly journals Potential Clinical Applications for Human Pluripotent Stem Cell-Derived Blood Components

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Erin A. Kimbrel ◽  
Shi-Jiang Lu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Large Scale ◽  
Embryonic Stem ◽  
Adult Stem Cell ◽  
Cell Types ◽  
The Body ◽  
Blood Components ◽  
Induced Pluripotent

The ability of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) to divide indefinitely without losing pluripotency and to theoretically differentiate into any cell type in the body makes them highly attractive cell sources for large scale regenerative medicine purposes. The current use of adult stem cell-derived products in hematologic intervention sets an important precedent and provides a guide for developing hESC/iPSC based therapies for the blood system. In this review, we highlight biological functions of mature cells of the blood, clinical conditions requiring the transfusion or stimulation of these cells, and the potential for hESC/iPSC-derivatives to serve as functional replacements. Many researchers have already been able to differentiate hESCs and/or iPSCs into specific mature blood cell types. For example, hESC-derived red blood cells and platelets are functional in tasks such as oxygen delivery and blood clotting, respectively and may be able to serve as substitutes for their donor-derived counterparts in emergencies. hESC-derived dendritic cells are functional in antigen-presentation and may be used as off-the-shelf vaccine therapies to stimulate antigen-specific immune responses against cancer cells. However,in vitrodifferentiation systems used to generate these cells will need further optimization before hESC/iPSC-derived blood components can be used clinically.

scholarly journals Is Stem Cell a Curer or an Obstruction?

2017 ◽  
Vol 1 (1) ◽  
pp. 17
Author(s):  
Siska Damayanti ◽  
Rina Triana ◽  
Angliana Chouw ◽  
Nurrani Mustika Dewi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Embryonic Stem ◽  
Cell Types ◽  
Tumor Formation ◽  
The Body ◽  
Negative Effects ◽  
Tissue Repair And Regeneration

Introduction: Each cell in human body is assigned with a specialized function to perform.  Before a cell becomes specialized, it is a stem cell. Stem cell research and therapy is progressing dramatically these days. Stem cell therapy holds enormous treatment potential for many diseases which currently have no or limited therapeutic options. Unfortunately, this potential also comes with side-effects. In this review, the positive and negative effects of regulation of stem cells will be explained.Content: Stem cells are undifferentiated cells that have potential to develop into many different cell types in the body during early life and growth. The type of stem cells are embryonic stem cells, induced pluripotent stem cells, somatic stem cells, foetal stem cells and mesenchymal stem cells. Stem cell transplantation is one form of stem cell therapy, it comes with different sources, and those are autologous and allogenic transplantation stem cells. In an autologous transplant, a patient’s own blood-forming stem cells are collected, meanwhile in an allogeneic transplant, a person’s stem cells are replaced with new stem cells obtained from a donor or from donated umbilical cord blood.Summary: Its abilities to maintain undifferentiated phenotype, self-renewing and differentiate itself into specialized cells, give rise to stem cell as a new innovation for the treatment of various diseases. In the clinical setting, stem cells are being explored in various conditions, such as in tissue repair and regeneration and autoimmune diseases therapy. But along with its benefit, stem cell therapy also holds some harm. It is known that the treatment using stem cell for curing and rehabilitation has the risk in tumor formation.

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

Sign in / Sign up

Export Citation Format

Share Document