scholarly journals Aneuploidy in intestinal stem cells promotes gut dysplasia in Drosophila

2018 ◽  
Vol 217 (11) ◽  
pp. 3930-3946 ◽  
Author(s):  
Luís Pedro Resende ◽  
Augusta Monteiro ◽  
Rita Brás ◽  
Tatiana Lopes ◽  
Claudio E. Sunkel

Aneuploidy is associated with different human diseases including cancer. However, different cell types appear to respond differently to aneuploidy, either by promoting tumorigenesis or causing cell death. We set out to study the behavior of adult Drosophila melanogaster intestinal stem cells (ISCs) after induction of chromosome missegregation either by abrogation of the spindle assembly checkpoint or through kinetochore disruption or centrosome amplification. These conditions induce moderate levels of aneuploidy in ISCs, and we find no evidence of apoptosis. Instead, we observe a significant accumulation of ISCs associated with increased stem cell proliferation and an excess of enteroendocrine cells. Moreover, aneuploidy causes up-regulation of the JNK pathway throughout the posterior midgut, and specific inhibition of JNK signaling in ISCs is sufficient to prevent dysplasia. Our findings highlight the importance of understanding the behavior of different stem cell populations to aneuploidy and how these can act as reservoirs for genomic alterations that can lead to tissue pathologies.

2015 ◽  
Vol 208 (6) ◽  
pp. 807-819 ◽  
Author(s):  
Aiguo Tian ◽  
Qing Shi ◽  
Alice Jiang ◽  
Shuangxi Li ◽  
Bing Wang ◽  
...  

Many adult tissues are maintained by resident stem cells that elevate their proliferation in response to injury. The regulatory mechanisms underlying regenerative proliferation are still poorly understood. Here we show that injury induces Hedgehog (Hh) signaling in enteroblasts (EBs) to promote intestinal stem cell (ISC) proliferation in Drosophila melanogaster adult midgut. Elevated Hh signaling by patched (ptc) mutations drove ISC proliferation noncell autonomously. Inhibition of Hh signaling in the ISC lineage compromised injury-induced ISC proliferation but had little if any effect on homeostatic proliferation. Hh signaling acted in EBs to regulate the production of Upd2, which activated the JAK–STAT pathway to promote ISC proliferation. Furthermore, we show that Hh signaling is stimulated by DSS through the JNK pathway and that inhibition of Hh signaling in EBs prevented DSS-stimulated ISC proliferation. Hence, our study uncovers a JNK–Hh–JAK–STAT signaling axis in the regulation of regenerative stem cell proliferation.


2017 ◽  
Vol 217 (1) ◽  
pp. 79-92 ◽  
Author(s):  
Brice E. Keyes ◽  
Elaine Fuchs

Stem cells are imbued with unique qualities. They have the capacity to propagate themselves through symmetric divisions and to divide asymmetrically to engender new cells that can progress to differentiate into tissue-specific, terminal cell types. Armed with these qualities, stem cells in adult tissues are tasked with replacing decaying cells and regenerating tissue after injury to maintain optimal tissue function. With increasing age, stem cell functional abilities decline, resulting in reduced organ function and delays in tissue repair. Here, we review the effect of aging in five well-studied adult murine stem cell populations and explore age-related declines in stem cell function and their consequences for stem cell self-renewal, tissue homeostasis, and regeneration. Finally, we examine transcriptional changes that have been documented in aged stem cell populations and discuss new questions and future directions that this collection of data has uncovered.


Nanoscale ◽  
2017 ◽  
Vol 9 (28) ◽  
pp. 9848-9858 ◽  
Author(s):  
Maria del Mar Encabo-Berzosa ◽  
Maria Sancho-Albero ◽  
Alejandra Crespo ◽  
Vanesa Andreu ◽  
Victor Sebastian ◽  
...  

Mesenchymal stem cells (MSCs) not only can be differentiated into different cell types but also have tropism towards injured or inflamed tissues serving as repair cells.


2015 ◽  
Vol 03 (02) ◽  
pp. 060-065
Author(s):  
Marry Singla ◽  
Vinay Dua ◽  
A Reddy ◽  

AbstractRecent studies suggest that Stem Cells being used for a number of regenerative diseases. Stem cells can self-renew and produce different cell types, thus providing new strategies to regenerate missing tissues and treat diseases. In the field of dentistry, adult mesenchymal stem/stromal cells (MSCs) have been identified in several oral tissues, which suggests that the oral tissues are a rich source of stem cells, and oral stem and mucosal cells are expected to provide an ideal source for genetically reprogrammed cells such as induced pluripotent stem (IPS) cells. Furthermore, oral tissues are expected to be not only a source but also a therapeutic target for stem cells, as stem cell and tissue engineering therapies in dentistry continue to attract increasing clinical interest. With appropriate biochemical signals stem cells can be transformed into desirable cells. The idea behind this article is to shortly review the obtained literature on stem cell with respect to their properties, types and advantages of dental stem cells. Emphasis has been given to the possibilities of stem cell therapy including regeneration of tooth and craniofacial defects.


2018 ◽  
Author(s):  
Luís Pedro Resende ◽  
Augusta Monteiro ◽  
Rita Brás ◽  
Tatiana Lopes ◽  
Claudio E. Sunkel

AbstractAneuploidy is associated with different human diseases, particularly cancer, but how different cell types within tissues respond to aneuploidy is not fully understood. In some studies, aneuploidy has been shown to have a deleterious effect and lead to cell death, however it has also been shown to be a causal event of tumorigenesis in other contexts.Here, we show that Drosophila intestinal stem cells have a particular tolerance to aneuploidy and do not activate apoptosis in response to chromosome misegregation like other non-stem cells. Instead, we observe the development of tissue dysplasia characterized by an accumulation of progenitor cells, increased stem cell proliferation rate, and an excess of cells of the enteroendocrine lineage. Our findings highlight the importance of mechanisms acting to prevent aneuploidy within tissue stem cells and provide an in vivo model of how these cells can act as reservoirs for genomic alterations that can lead to dysplasia.


Author(s):  
Prithiv K R Kumar

Renal failure is a major health problem. The mortality rate remain high despite of several therapies. The most complex of the renal issues are solved through stem cells. In this review, different mechanism for cure of chronic kidney injury along with cell engraftment incorporated into renal structures will be analysed. Paracrine activities of embryonic or induced Pluripotent stem cells are explored on the basis of stem cell-induced kidney regeneration. Several experiments have been conducted to advance stem cells to ensure the restoration of renal functions. More vigour and organised protocols for delivering stem cells is a possibility for advancement in treatment of renal disease. Also there is a need for pressing therapies to replicate the tissue remodelling and cellular repair processes suitable for renal organs. Stem cells are the undifferentiated cells that have the ability to multiply into several cell types. In vivo experiments on animal’s stem cells have shown significant improvements in the renal regeneration and functions of organs. Nevertheless more studies show several improvements in the kidney repair due to stem cell regeneration.


2021 ◽  
Vol 22 (2) ◽  
pp. 666
Author(s):  
Toshio Takahashi

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.


Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1074
Author(s):  
Giuseppina Divisato ◽  
Silvia Piscitelli ◽  
Mariantonietta Elia ◽  
Emanuela Cascone ◽  
Silvia Parisi

Embryonic stem cells (ESCs) have the extraordinary properties to indefinitely proliferate and self-renew in culture to produce different cell progeny through differentiation. This latter process recapitulates embryonic development and requires rounds of the epithelial–mesenchymal transition (EMT). EMT is characterized by the loss of the epithelial features and the acquisition of the typical phenotype of the mesenchymal cells. In pathological conditions, EMT can confer stemness or stem-like phenotypes, playing a role in the tumorigenic process. Cancer stem cells (CSCs) represent a subpopulation, found in the tumor tissues, with stem-like properties such as uncontrolled proliferation, self-renewal, and ability to differentiate into different cell types. ESCs and CSCs share numerous features (pluripotency, self-renewal, expression of stemness genes, and acquisition of epithelial–mesenchymal features), and most of them are under the control of microRNAs (miRNAs). These small molecules have relevant roles during both embryogenesis and cancer development. The aim of this review was to recapitulate molecular mechanisms shared by ESCs and CSCs, with a special focus on the recently identified classes of microRNAs (noncanonical miRNAs, mirtrons, isomiRs, and competitive endogenous miRNAs) and their complex functions during embryogenesis and cancer development.


Author(s):  
Anja Trillhaase ◽  
Marlon Maertens ◽  
Zouhair Aherrahrou ◽  
Jeanette Erdmann

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


2021 ◽  
Vol 22 (13) ◽  
pp. 7043
Author(s):  
Shaida Ouladan ◽  
Alex Gregorieff

Despite the environmental constraints imposed upon the intestinal epithelium, this tissue must perform essential functions such as nutrient absorption and hormonal regulation, while also acting as a critical barrier to the outside world. These functions depend on a variety of specialized cell types that are constantly renewed by a rapidly proliferating population of intestinal stem cells (ISCs) residing at the base of the crypts of Lieberkühn. The niche components and signals regulating crypt morphogenesis and maintenance of homeostatic ISCs have been intensely studied over the last decades. Increasingly, however, researchers are turning their attention to unraveling the mechanisms driving gut epithelial regeneration due to physical damage or infection. It is now well established that injury to the gut barrier triggers major cell fate changes, demonstrating the highly plastic nature of the gut epithelium. In particular, lineage tracing and transcriptional profiling experiments have uncovered several injury-induced stem-cell populations and molecular markers of the regenerative state. Despite the progress achieved in recent years, several questions remain unresolved, particularly regarding the mechanisms driving dedifferentiation of the gut epithelium. In this review, we summarize the latest studies, primarily from murine models, that define the regenerative processes governing the gut epithelium and discuss areas that will require more in-depth investigation.


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