scholarly journals Cancer Stem Cells: Repair Gone Awry?

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Fatima Rangwala ◽  
Alessia Omenetti ◽  
Anna Mae Diehl

Because cell turnover occurs in all adult organs, stem/progenitor cells within the stem-cell niche of each tissue must be appropriately mobilized and differentiated to maintain normal organ structure and function. Tissue injury increases the demands on this process, and thus may unmask defective regulation of pathways, such as Hedgehog (Hh), that modulate progenitor cell fate. Hh pathway dysregulation has been demonstrated in many types of cancer, including pancreatic and liver cancers, in which defective Hh signaling has been linked to outgrowth of Hh-responsive cancer stem-initiating cells and stromal elements. Hence, the Hh pathway might be a therapeutic target in such tumors.

2018 ◽  
Vol 115 (46) ◽  
pp. 11838-11843 ◽  
Author(s):  
Eleonore Holzwart ◽  
Apolonio Ignacio Huerta ◽  
Nina Glöckner ◽  
Borja Garnelo Gómez ◽  
Friederike Wanke ◽  
...  

Multicellularity arose independently in plants and animals, but invariably requires a robust determination and maintenance of cell fate that is adaptive to the environment. This is exemplified by the highly specialized water- and nutrient-conducting cells of the plant vasculature, the organization of which is already prepatterned close to the stem-cell niche, but can be modified according to extrinsic cues. Here, we show that the hormone receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) is required for root vascular cell-fate maintenance, as BRI1 mutants show ectopic xylem in procambial position. However, this phenotype seems unrelated to canonical brassinosteroid signaling outputs. Instead, BRI1 is required for the expression and function of its interacting partner RECEPTOR-LIKE PROTEIN 44 (RLP44), which, in turn, associates with the receptor for the peptide hormone phytosulfokine (PSK). We show that PSK signaling is required for the maintenance of procambial cell identity and quantitatively controlled by RLP44, which promotes complex formation between the PSK receptor and its coreceptor. Mimicking the loss of RLP44, PSK-related mutants show ectopic xylem in the position of the procambium, whereas rlp44 is rescued by exogenous PSK. Based on these findings, we propose that RLP44 controls cell fate by connecting BRI1 and PSK signaling, providing a mechanistic framework for the dynamic balancing of signaling mediated by the plethora of plant receptor-like kinases at the plasma membrane.


2016 ◽  
Vol 38 (5) ◽  
pp. 548-566 ◽  
Author(s):  
Freyja K. McClenahan ◽  
Himanshu Sharma ◽  
Xiwei Shan ◽  
Christopher Eyermann ◽  
Holly Colognato

2021 ◽  
Vol 12 ◽  
Author(s):  
Mónica L. García-Gómez ◽  
Adriana Garay-Arroyo ◽  
Berenice García-Ponce ◽  
María de la Paz Sánchez ◽  
Elena R. Álvarez-Buylla

The root stem cell niche (SCN) of Arabidopsis thaliana consists of the quiescent center (QC) cells and the surrounding initial stem cells that produce progeny to replenish all the tissues of the root. The QC cells divide rather slowly relative to the initials, yet most root tissues can be formed from these cells, depending on the requirements of the plant. Hormones are fundamental cues that link such needs with the cell proliferation and differentiation dynamics at the root SCN. Nonetheless, the crosstalk between hormone signaling and the mechanisms that regulate developmental adjustments is still not fully understood. Developmental transcriptional regulatory networks modulate hormone biosynthesis, metabolism, and signaling, and conversely, hormonal responses can affect the expression of transcription factors involved in the spatiotemporal patterning at the root SCN. Hence, a complex genetic–hormonal regulatory network underlies root patterning, growth, and plasticity in response to changing environmental conditions. In this review, we summarize the scientific literature regarding the role of hormones in the regulation of QC cell proliferation and discuss how hormonal signaling pathways may be integrated with the gene regulatory network that underlies cell fate in the root SCN. The conceptual framework we present aims to contribute to the understanding of the mechanisms by which hormonal pathways act as integrators of environmental cues to impact on SCN activity.


2013 ◽  
Vol 2013 ◽  
pp. 1-7
Author(s):  
Jessica M. Gluck ◽  
Jennifer Chyu ◽  
Connor Delman ◽  
Sepideh Heydarkhan-Hagvall ◽  
W. Robb MacLellan ◽  
...  

The relationship between stem cell niches in vivo and their surrounding microenvironment is still relatively unknown. Recent advances have indicated that extrinsic factors within the cardiovascular progenitor cell niche influence maintenance of a multipotent state as well as drive cell-fate decisions. We have previously shown the direct effects of extracellular matrix (ECM) proteins and have now investigated the effects of dimension on the induction of a cardiovascular progenitor cell (CPC) population. We have shown here that the three-dimensionality of a hyaluronan-based hydrogel greatly induces a CPC population, as marked by Flk-1. We have compared the effects of a 3D microenvironment to those of conventional 2D cell culture practices and have found that the 3D microenvironment potently induces a progenitor cell state.


Author(s):  
Geoffrey Bellingan ◽  
Brijesh V. Patel

Inflammation is the beneficial host response to foreign challenge or tissue injury that ultimately leads to the restoration of tissue structure and function. Critical illness is associated with an overwhelming and prolonged inflammatory activation. Resolution of the inflammatory response is an active process that requires removal of the inciting stimuli, cessation of the pro-inflammatory response, a timely coordinated removal of tissue leukocyte infiltration, a conversion from ‘toxic’ to reparative tissue environment, and restoration of normal tissue structure and function. Mortality may result from deficits in these resolution mechanisms. Improved delivery of critical care through prevention of harm and removal of stimuli has already delivered significant mortality benefits. Most critically-ill patients present with uncontrolled inflammation, hence anti-inflammatory strategies ameliorating this response are likely to be too late and thus futile. Rather, strategies augmenting endogenous pathways involved in the control and appropriate curtailment of such inflammatory responses may promote resolution, repair, and catabasis. Recent evidence showing that inflammation does not simply ‘fizzle out’, but its resolution involves an active and coordinated series of events. Dysfunction of these resolution checkpoints alters the normal inflammatory pathway, and is implicated in the induction and maintenance of states such as ARDS and sepsis. Improved understanding of resolution biology should provide translational pathways to not only improve survival, but also to prevent long-term morbidity resulting from tissue damage.


Blood ◽  
2010 ◽  
Vol 116 (11) ◽  
pp. 1857-1866 ◽  
Author(s):  
Ilaria Visigalli ◽  
Silvia Ungari ◽  
Sabata Martino ◽  
Hyejung Park ◽  
Martina Cesani ◽  
...  

Abstract The balance between survival and death in many cell types is regulated by small changes in the intracellular content of bioactive sphingolipids. Enzymes that either produce or degrade these sphingolipids control this equilibrium. The findings here described indicate that the lysosomal galactocerebrosidase (GALC) enzyme, defective in globoid cell leukodystrophy, is involved in the maintenance of a functional hematopoietic stem/progenitor cell (HSPC) niche by contributing to the control of the intracellular content of key sphingolipids. Indeed, we show that both insufficient and supraphysiologic GALC activity—by inherited genetic deficiency or forced gene expression in patients' cells and in the disease model—induce alterations of the intracellular content of the bioactive GALC downstream products ceramide and sphingosine, and thus affect HSPC survival and function and the functionality of the stem cell niche. Therefore, GALC and, possibly, other enzymes for the maintenance of niche functionality and health tightly control the concentration of these sphingolipids within HSPCs.


2020 ◽  
Author(s):  
Clara Becker ◽  
Katharina Lust ◽  
Joachim Wittbrodt

AbstractBalancing the relative growth of body and organs is of key importance for coordinating size and function. This is of particular relevance in post-embryonically growing organisms, facing this challenge life-long. We addressed this question in the neuroretina of medaka fish (Oryzias latipes), where growth and size regulation are crucial for functional homeostasis of the visual system. We find that a central growth regulator, Igf1 receptor, is necessary and sufficient for proliferation control in the postembryonic retinal stem cell niche, the ciliary marginal zone (CMZ). Targeted activation of Igf1r signalling in the CMZ uncouples neuroretina growth from body size control, increasing layer thickness while preserving the structural integrity of the retina. The retinal expansion is driven exclusively by enhanced proliferation of progenitor cells while stem cells do not respond to Igf1r modulation. Our findings position Igf signalling as key module controlling retinal size and structure with far reaching evolutionary implications.


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