Role of Rho GTPases in stem cell regulation

2021 ◽  
Author(s):  
Zheng Zhang ◽  
Ming Liu ◽  
Yi Zheng
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Embryonic Stem ◽  
Cell Types ◽  
Tissue Homeostasis ◽  
Cell Manipulation ◽  
Stem Cell Regulation

The future of regenerative medicine relies on our understanding of stem cells which are essential for tissue/organ generation and regeneration to maintain and/or restore tissue homeostasis. Rho family GTPases are known regulators of a wide variety of cellular processes related to cytoskeletal dynamics, polarity and gene transcription. In the last decade, major new advances have been made in understanding the regulatory role and mechanism of Rho GTPases in self-renewal, differentiation, migration, and lineage specification in tissue-specific signaling mechanisms in various stem cell types to regulate embryonic development, adult tissue homeostasis, and tissue regeneration upon stress or damage. Importantly, implication of Rho GTPases and their upstream regulators or downstream effectors in the transformation, migration, invasion and tumorigenesis of diverse cancer stem cells highlights the potential of Rho GTPase targeting in cancer therapy. In this review, we discuss recent evidence of Rho GTPase signaling in the regulation of embryonic stem cells, multiple somatic stem cells, and cancer stem cells. We propose promising areas where Rho GTPase pathways may serve as useful targets for stem cell manipulation and related future therapies.

scholarly journals Multiple Roles for Cholinergic Signaling from the Perspective of Stem Cell Function

2021 ◽  
Vol 22 (2) ◽  
pp. 666
Author(s):  
Toshio Takahashi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Function ◽  
Cell Activity ◽  
Embryonic Stem ◽  
Cholinergic Neurons ◽  
Cell Types ◽  
Proliferative Potential ◽  
True Nature ◽  
Cholinergic Signaling

Stem cells have extensive proliferative potential and the ability to differentiate into one or more mature cell types. The mechanisms by which stem cells accomplish self-renewal provide fundamental insight into the origin and design of multicellular organisms. These pathways allow the repair of damage and extend organismal life beyond that of component cells, and they probably preceded the evolution of complex metazoans. Understanding the true nature of stem cells can only come from discovering how they are regulated. The concept that stem cells are controlled by particular microenvironments, also known as niches, has been widely accepted. Technical advances now allow characterization of the zones that maintain and control stem cell activity in several organs, including the brain, skin, and gut. Cholinergic neurons release acetylcholine (ACh) that mediates chemical transmission via ACh receptors such as nicotinic and muscarinic receptors. Although the cholinergic system is composed of organized nerve cells, the system is also involved in mammalian non-neuronal cells, including stem cells, embryonic stem cells, epithelial cells, and endothelial cells. Thus, cholinergic signaling plays a pivotal role in controlling their behaviors. Studies regarding this signal are beginning to unify our understanding of stem cell regulation at the cellular and molecular levels, and they are expected to advance efforts to control stem cells therapeutically. The present article reviews recent findings about cholinergic signaling that is essential to control stem cell function in a cholinergic niche.

scholarly journals Induced Pluripotent Stem Cells (iPSCs) in Vascular Research: from Two- to Three-Dimensional Organoids

2021 ◽  
Author(s):  
Anja Trillhaase ◽  
Marlon Maertens ◽  
Zouhair Aherrahrou ◽  
Jeanette Erdmann
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Induced Pluripotent Stem Cells ◽  
Stem Cell Research ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
3D Models ◽  
Induced Pluripotent

AbstractStem cell technology has been around for almost 30 years and in that time has grown into an enormous field. The stem cell technique progressed from the first successful isolation of mammalian embryonic stem cells (ESCs) in the 1990s, to the production of human induced-pluripotent stem cells (iPSCs) in the early 2000s, to finally culminate in the differentiation of pluripotent cells into highly specialized cell types, such as neurons, endothelial cells (ECs), cardiomyocytes, fibroblasts, and lung and intestinal cells, in the last decades. In recent times, we have attained a new height in stem cell research whereby we can produce 3D organoids derived from stem cells that more accurately mimic the in vivo environment. This review summarizes the development of stem cell research in the context of vascular research ranging from differentiation techniques of ECs and smooth muscle cells (SMCs) to the generation of vascularized 3D organoids. Furthermore, the different techniques are critically reviewed, and future applications of current 3D models are reported. Graphical abstract

Types of Stem Cells Used in US-Based Clinical Trials between 1999 and 2014

2021 ◽  
Vol 26 ◽  
pp. 169-191
Author(s):  
Emma E. Redfield ◽  
Erin K. Luciano ◽  
Monica J. Sewell ◽  
Lucas A. Mitzel ◽  
Isaac J. Sanford ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
The Us ◽  
Health Database ◽  
Induced Pluripotent

This study looks at the number of clinical trials involving specific stem cell types. To our knowledge, this has never been done before. Stem cell clinical trials that were conducted at locations in the US and registered on the National Institutes of Health database at ‘clinicaltrials.gov’ were categorized according to the type of stem cell used (adult, cancer, embryonic, perinatal, or induced pluripotent) and the year that the trial was registered. From 1999 to 2014, there were 2,357 US stem cell clinical trials registered on ‘clinicaltrials.gov,’ and 89 percent were from adult stem cells and only 0.12 percent were from embryonic stem cells. This study concludes that embryonic stem cells should no longer be used for clinical study because of their irrelevance, moral questions, and induced pluripotent stem cells.

scholarly journals Regulation of Prostatic Stem Cells by Stromal Niche in Health and Disease

Endocrinology ◽  
2008 ◽  
Vol 149 (9) ◽  
pp. 4303-4306 ◽  
Author(s):  
Gail P. Risbridger ◽  
Renea A. Taylor
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Tumor Stroma ◽  
Stem Cell Differentiation ◽  
Stem Cell Regulation ◽  
Isolation And Characterization ◽  
Tissue Recombination ◽  
Cell Niche

The isolation and characterization of prostatic stem cells has received significant attention in the last few years based on the belief that aberrant regulation of adult stem cells leads to prostate disease including cancer. The nature of the perturbations in stem cell regulation remains largely unknown. Although adult stem cells are can be governed by autonomous regulatory mechanisms, the stromal niche environment also provides essential cues to direct directing differentiation decisions and can lead to aberrant proliferation and/or differentiation. Elegant tissue recombination experiments, pioneered by Gerald Cunha and colleagues, provided evidence that quiescent epithelial tissues containing adult stem cells were capable of altered differentiation in response to inductive and instructive mesenchyme. In more recent times, it has been demonstrated that embryonic mesenchyme is sufficiently powerful to direct the differentiation of embryonic stem cells into mature prostate or bladder. In addition, prostatic tumor stroma provides another unique niche or microenvironment for stem cell differentiation that is distinct to normal stroma. This review highlights the importance of the appropriate selection of the stromal cell niche for tissue regeneration and implies plasticity of adult stem cells that is dictated by the tissue microenvironment.

Stem Cells and Tissue Engineering Techniques

2013 ◽  
Vol 80 (1) ◽  
pp. 11-19
Author(s):  
Gigliola Sica
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Urinary Tract ◽  
Animal Models ◽  
Embryonic Stem ◽  
Cell Types ◽  
Ethical Concerns ◽  
Neoplastic Lesions

The therapeutic use of stem cells and tissue engineering techniques are emerging in urology. Here, stem cell types, their differentiating potential and fundamental characteristics are illustrated. The cancer stem cell hypothesis is reported with reference to the role played by stem cells in the origin, development and progression of neoplastic lesions. In addition, recent reports of results obtained with stem cells alone or seeded in scaffolds to overcome problems of damaged urinary tract tissue are summarized. Among others, the application of these biotechnologies in urinary bladder, and urethra are delineated. Nevertheless, apart from the ethical concerns raised from the use of embryonic stem cells, a lot of questions need to be solved concerning the biology of stem cells before their widespread use in clinical trials. Further investigation is also required in tissue engineering utilizing animal models.

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.

scholarly journals Two anatomically distinct niches regulate stem cell activity

Blood ◽  
2012 ◽  
Vol 120 (11) ◽  
pp. 2174-2181 ◽  
Author(s):  
Hideo Ema ◽  
Toshio Suda
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Cell Activity ◽  
Cell Types ◽  
Cell Number ◽  
Cell Regulation ◽  
Hematopoietic Stem ◽  
Stem Cell Regulation ◽  
Cellular Components

Abstract The niche microenvironment controls stem cell number, fate, and behavior. The bone marrow, intestine, and skin are organs with highly regenerative potential, and all produce a large number of mature cells daily. Here, focusing on adult stem cells in these organs, we compare the structures and cellular components of their niches and the factors they produce. We then define the niche as a functional unit for stem cell regulation. For example, the niche possibly maintains quiescence and regulates fate in stem cells. Moreover, we discuss our hypothesis that many stem cell types are regulated by both specialized and nonspecialized niches, although hematopoietic stem cells, as an exception, are regulated by a nonspecialized niche only. The specialized niche is composed of 1 or a few types of cells lying on the basement membrane in the epithelium. The nonspecialized niche is composed of various types of cells widely distributed in mesenchymal tissues. We propose that the specialized niche plays a role in local regulation of stem cells, whereas the nonspecialized niche plays a role in relatively broad regional or systemic regulation. Further work will verify this dual-niche model to understand mechanisms underlying stem cell regulation.

scholarly journals Conserved functional antagonism of CELF and MBNL proteins controls stem cell-specific alternative splicing in planarians

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Jordi Solana ◽  
Manuel Irimia ◽  
Salah Ayoub ◽  
Marta Rodriguez Orejuela ◽  
Vera Zywitza ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Alternative Splicing ◽  
Cell Biology ◽  
Embryonic Stem ◽  
In Vivo Model ◽  
Stem Cell Regulation ◽  
Specific Alternative ◽  
Functional Antagonism

In contrast to transcriptional regulation, the function of alternative splicing (AS) in stem cells is poorly understood. In mammals, MBNL proteins negatively regulate an exon program specific of embryonic stem cells; however, little is known about the in vivo significance of this regulation. We studied AS in a powerful in vivo model for stem cell biology, the planarian Schmidtea mediterranea. We discover a conserved AS program comprising hundreds of alternative exons, microexons and introns that is differentially regulated in planarian stem cells, and comprehensively identify its regulators. We show that functional antagonism between CELF and MBNL factors directly controls stem cell-specific AS in planarians, placing the origin of this regulatory mechanism at the base of Bilaterians. Knockdown of CELF or MBNL factors lead to abnormal regenerative capacities by affecting self-renewal and differentiation sets of genes, respectively. These results highlight the importance of AS interactions in stem cell regulation across metazoans.

209 Rho signaling-directed regulation of YAP/TAZ in parthenogenetic stem cells

2020 ◽  
Vol 32 (2) ◽  
pp. 233
Author(s):  
G. Pennarossa ◽  
S. Arcuri ◽  
F. Gandolfi ◽  
T. Brevini
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Rho Gtpase ◽  
Hippo Pathway ◽  
Genetic Material ◽  
Embryonic Stem ◽  
Cell Types ◽  
Embryonic Cell ◽  
And Migration ◽  
The Hippo Pathway

Mammalian oocyte maturation is characterised by asymmetric meiotic division that is regulated by specific cytoskeleton organisation. Similarly, during early embryonic divisions, one of the most important steps is the establishment of polarity that allows cells to adopt distinct developmental fates. All of these events are driven by dynamic changes in actin filaments. It has been demonstrated recently that the Rho signalling pathway plays a key role in the organisation and rearrangement of actin-containing structures, regulating cell polarity and migration. In addition, beside its effect on cell cytoskeleton, Rho directly interacts with the Hippo pathway, influencing both embryonic cell proliferation and differentiation. Because both Rho and Hippo are expressed by the oocyte and maternally inherited (Zhang et al. 2014 Cell Cycle 13, 3390-3403, https://doi.org/10.4161/15384101.2014.952967; Menchero et al. 2017 Dev. Dyn. 246, 245-261, https://doi.org/10.1002/dvdy.24471), we investigated their regulation in parthenogenetic embryonic stem cells (ParthESC) that possess exclusively maternal genetic material, and compared the results with biparental ESCs. Previous results obtained by whole-transcriptome analysis revealed the presence of several differentially expressed genes involved in the Rho pathway and showed no differences for most of the Hippo signalling genes. To better elucidate the molecular mechanisms involved, in the present study, we dissected the expression pattern of the Rho and Hippo regulatory genes in human biparental ESCs and ParthESC. Experiments were performed on 4 biparental ESC and 4 ParthESC lines using cells between passages 5 to 25. The results showed significantly increased transcription of the Rho GTPase family genes (RHOA, RHOB, and RHOC) in ParthESC compared with biparental ESCs. Consistent with this, 12 of 17 Rho activators were significantly upregulated, whereas 8 of 11 Rho inhibitors were significantly decreased in ParthESC. Furthermore, monoparental cells displayed significantly higher expression levels of YAP and TAZ, whereas the upstream genes involved in the Hippo pathway (LATS1/2, MOB1, MST1/2, NF2) were comparable in the two cell types. Interestingly, a significantly higher total YAP protein content was detected in ParthESC, whereas the quantity of the phosphorylated form was comparable in the two cell types. This accounts for the observed upregulation of Rho genes, which stimulate the assembly of contractile actin stress fibres, inhibiting LATS1/2 phosphorylation and preventing subsequent phosphorylation of YAP/TAZ (Yu and Guan 2013 Genes Dev. 27, 355-371; https://doi.org/10.1101/gad.210773.112). Altogether, our results suggest that the Rho pathway may regulate YAP/TAZ behaviour via a LATS/MST/NF2-independent process in ParthESC, similarly to a previous report in oocytes (Posfai and Rossant 2016 Cell Res. 26, 393-394; https://doi.org/10.1038/cr.2016). Although further clarifications are needed, we hypothesise that the regulatory mechanisms detected in ParthESC may be related to their strictly maternal origin, with a possible impact on their plasticity and potency. This study was supported by Carraresi Foundation. Authors are members of the COST Actions CA16119.

Exploring the role of stem cell therapy in treating neurodegenerative diseases: Challenges and current perspectives

2021 ◽  
Vol 16 ◽  
Author(s):  
Nidhi Puranik ◽  
Ananta Prasad Arukha ◽  
Shiv Kumar Yadav ◽  
Dhananjay Yadav ◽  
Jun O Jin
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Glial Cells ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Embryonic Stem ◽  
Cell Types ◽  
Cell Based Therapy ◽  
Promising Therapeutic Approach ◽  
Cord Injury

: Several human neurological disorders such as Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis; Huntington’s disease, spinal cord injury, multiple sclerosis, and brain stroke, are caused by the injury to neurons or glial cells. The recent years have witnessed the successful generation of neurons and glia cells driving efforts to develop stem-cell-based therapies for patients to combat a broad spectrum of human neurological diseases. The inadequacy of suitable cell types for cell replacement therapy in patients suffering from neurological disorders have hampered the development of this promising therapeutic approach. Attempts are thus being made to reconstruct viable neurons and glial cells from different stem cells such as the embryonic stem cells, mesenchymal stem cells, and neural stem cells. Dedicated research to cultivate stem cell-based brain transplantation therapies have been carried out. We aim at compiling the breakthroughs in the field of stem cell-based therapy for the treatment of neurodegenerative maladies, emphasizing on the shortcomings faced, victories achieved, and the future prospects of the therapy in clinical settings.

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