scholarly journals Functions of Wnt and Hedgehog-containing extracellular vesicles in development and disease

2020 ◽  
Vol 133 (18) ◽  
pp. jcs209742
Author(s):  
Tamás Matusek ◽  
Julien Marcetteau ◽  
Pascal P. Thérond
Keyword(s):  
Cell Fate ◽  
Extracellular Vesicles ◽  
Extracellular Space ◽  
Control Cell ◽  
Model Organisms ◽  
Membrane Bilayer ◽  
Animal Development ◽  
High Affinity ◽  
Mechanisms Of Formation ◽  
And Control

ABSTRACTSecreted morphogens play a major role in the intercellular communication necessary for animal development. It was initially thought that, in order to organize tissue morphogenesis and control cell fate and proliferation, morphogens diffused freely in the extracellular space. This view has since changed following the discovery that morphogens of the Wnt and Hedgehog (Hh) families are modified by various lipid adducts during their biosynthesis, providing them with high affinity for the membrane bilayer. Recent work performed in model organisms suggests that Wnt and Hh proteins are carried on extracellular vesicles. In this Review, we provide our perspectives on the mechanisms of formation of Wnt- and Hh-containing extracellular vesicles, and discuss their functions during animal development, as well as in various human physiopathologies.

The ataxia‐telangiectasia gene product may modulate DNA turnover and control cell fate by regulating cellular redox in lymphocytes

2001 ◽  
Vol 15 (7) ◽  
pp. 1132-1138 ◽  
Author(s):  
MINGSHAN YAN ◽  
WENAN QIANG ◽  
NA LIU ◽  
JIANJUN SHEN ◽  
WILLIAM S. LYNN ◽  
...  
Keyword(s):  
Gene Product ◽  
Cell Fate ◽  
Ataxia Telangiectasia ◽  
Control Cell ◽  
Cellular Redox ◽  
Dna Turnover ◽  
And Control

scholarly journals Coordinating cell polarity and cell cycle progression: what can we learn from flies and worms?

Open Biology ◽  
2013 ◽  
Vol 3 (8) ◽  
pp. 130083 ◽  
Author(s):  
Anna Noatynska ◽  
Nicolas Tavernier ◽  
Monica Gotta ◽  
Lionel Pintard
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Fate ◽  
Cell Polarity ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Asymmetric Cell Division ◽  
Control Cell ◽  
Model Organisms ◽  
Cycle Progression

Spatio-temporal coordination of events during cell division is crucial for animal development. In recent years, emerging data have strengthened the notion that tight coupling of cell cycle progression and cell polarity in dividing cells is crucial for asymmetric cell division and ultimately for metazoan development. Although it is acknowledged that such coupling exists, the molecular mechanisms linking the cell cycle and cell polarity machineries are still under investigation. Key cell cycle regulators control cell polarity, and thus influence cell fate determination and/or differentiation, whereas some factors involved in cell polarity regulate cell cycle timing and proliferation potential. The scope of this review is to discuss the data linking cell polarity and cell cycle progression, and the importance of such coupling for asymmetric cell division. Because studies in model organisms such as Caenorhabditis elegans and Drosophila melanogaster have started to reveal the molecular mechanisms of this coordination, we will concentrate on these two systems. We review examples of molecular mechanisms suggesting a coupling between cell polarity and cell cycle progression.

scholarly journals Characterization of the Skeletal Muscle Secretome Reveals a Role for Extracellular Vesicles and IL1α/IL1β in Restricting Fibro/Adipogenic Progenitor Adipogenesis

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1171
Author(s):  
Simone Vumbaca ◽  
Giulio Giuliani ◽  
Valeria Fiorentini ◽  
Flavia Tortolici ◽  
Andrea Cerquone Perpetuini ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cell Fate ◽  
Extracellular Vesicles ◽  
Muscle Regeneration ◽  
Adipogenic Differentiation ◽  
Control Cell ◽  
Regeneration Process ◽  
Adult Skeletal Muscle ◽  
Pathological Conditions ◽  
Cell Cell

Repeated mechanical stress causes injuries in the adult skeletal muscle that need to be repaired. Although muscle regeneration is a highly efficient process, it fails in some pathological conditions, compromising tissue functionality. This may be caused by aberrant cell–cell communication, resulting in the deposition of fibrotic and adipose infiltrates. Here, we investigate in vivo changes in the profile of skeletal muscle secretome during the regeneration process to suggest new targetable regulatory circuits whose failure may lead to tissue degeneration in pathological conditions. We describe the kinetic variation of expression levels of 76 secreted proteins during the regeneration process. In addition, we profile the gene expression of immune cells, endothelial cells, satellite cells, and fibro-adipogenic progenitors. This analysis allowed us to annotate each cell-type with the cytokines and receptors they have the potential to synthetize, thus making it possible to draw a cell–cell interaction map. We next selected 12 cytokines whose receptors are expressed in FAPs and tested their ability to modulate FAP adipogenesis and proliferation. We observed that IL1α and IL1β potently inhibit FAP adipogenesis, while EGF and BTC notably promote FAP proliferation. In addition, we characterized the cross-talk mediated by extracellular vesicles (EVs). We first monitored the modulation of muscle EV cargo during tissue regeneration. Using a single-vesicle flow cytometry approach, we observed that EVs differentially affect the uptake of RNA and proteins into their lumen. We also investigated the EV capability to interact with SCs and FAPs and to modulate their proliferation and differentiation. We conclude that both cytokines and EVs secreted during muscle regeneration have the potential to modulate adipogenic differentiation of FAPs. The results of our approach provide a system-wide picture of mechanisms that control cell fate during the regeneration process in the muscle niche.

Precise selection of aptamers targeting PD-L1 positive small extracellular vesicles on magnetic chips

2021 ◽  
Vol 57 (29) ◽  
pp. 3555-3558
Author(s):  
Hao-Yu Dong ◽  
Qi-Hui Xie ◽  
Dai-Wen Pang ◽  
Gang Chen ◽  
Zhi-Ling Zhang
Keyword(s):  
Extracellular Vesicles ◽  
High Affinity ◽  
Selection Of

High affinity aptamers that target small extracellular vesicles displaying PD-L1 in its natural conformation were successfully selected.

scholarly journals Cord Blood Extracellular Vesicles Analyzed by Flow Cytometry with Thresholding Using 405 nm or 488 nm Laser Leads to Concurrent Results

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1320
Author(s):  
Kristýna Pekárková ◽  
Jakub Soukup ◽  
Marie Kostelanská ◽  
Jan Širc ◽  
Zbyněk Straňák ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cord Blood ◽  
Extracellular Vesicles ◽  
Correlation Coefficients ◽  
Flow Cytometer ◽  
Liquid Biopsies ◽  
Physiological Conditions ◽  
Flow Cytometric ◽  
Term Births ◽  
And Control

Extracellular vesicles (EVs) from liquid biopsies are extensively analyzed by flow cytometry, a technology that is continuously evolving. Thresholding utilizing a violet 405 nm laser side scatter (VSSC) has recently been implemented. Here, we collected set of large EV (lEV) samples from cord blood, which we analyzed using a standard flow cytometer improved via a 405 nm laser side scatter. Samples were analyzed using two distinct thresholding methods—one based on VSSC, and one based on VSSC combined with fluorescence thresholding on stained phosphatidylserine. Through these thresholding methods, we compared lEVs from pre-term births and control cord blood. Double-labeled lEVs with platelet CD36+/CD41+, activated platelet CD41+/CD62P+ and endothelial CD31+/CD105+ antibodies were used. Apart from comparing the two groups together, we also correlated measured lEVs with the thresholding methods. We also correlated the results of this study with data analyzed in our previous study in which we used a conventional 488 nm laser SSC. We did not find any difference between the two cord blood groups. However, we found highly concurrent data via our correlation of the thresholding methods, with correlation coefficients ranging from 0.80 to 0.96 even though the numbers of detected lEVs differed between thresholding methods. In conclusion, our approaches to thresholding provided concurrent data and it seems that improving the cytometer with the use of a VSSC increases its sensitivity, despite not being particularly critical to the validity of flow cytometric studies that compare pathological and physiological conditions in liquid biopsies.

scholarly journals Notch signaling coordinates ommatidial rotation in the Drosophila eye via transcriptional regulation of the EGF-Receptor ligand Argos

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yildiz Koca ◽  
Benjamin E. Housden ◽  
William J. Gault ◽  
Sarah J. Bray ◽  
Marek Mlodzik
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Planar Cell Polarity ◽  
Egf Receptor ◽  
Control Cell ◽  
Loss Of Function ◽  
Egfr Signaling ◽  
Specific Expression ◽  
Egfr Signaling Pathway ◽  
Ommatidial Rotation

AbstractIn all metazoans, a small number of evolutionarily conserved signaling pathways are reiteratively used during development to orchestrate critical patterning and morphogenetic processes. Among these, Notch (N) signaling is essential for most aspects of tissue patterning where it mediates the communication between adjacent cells to control cell fate specification. In Drosophila, Notch signaling is required for several features of eye development, including the R3/R4 cell fate choice and R7 specification. Here we show that hypomorphic alleles of Notch, belonging to the Nfacet class, reveal a novel phenotype: while photoreceptor specification in the mutant ommatidia is largely normal, defects are observed in ommatidial rotation (OR), a planar cell polarity (PCP)-mediated cell motility process. We demonstrate that during OR Notch signaling is specifically required in the R4 photoreceptor to upregulate the transcription of argos (aos), an inhibitory ligand to the epidermal growth factor receptor (EGFR), to fine-tune the activity of EGFR signaling. Consistently, the loss-of-function defects of Nfacet alleles and EGFR-signaling pathway mutants are largely indistinguishable. A Notch-regulated aos enhancer confers R4 specific expression arguing that aos is directly regulated by Notch signaling in this context via Su(H)-Mam-dependent transcription.

scholarly journals Positive Feedback Between PU.1 and the Cell Cycle Controls Myeloid Differentiation

Science ◽  
2013 ◽  
Vol 341 (6146) ◽  
pp. 670-673 ◽  
Author(s):  
Hao Yuan Kueh ◽  
Ameya Champhekar ◽  
Stephen L. Nutt ◽  
Michael B. Elowitz ◽  
Ellen V. Rothenberg
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Positive Feedback ◽  
Regulatory Gene ◽  
Control Cell ◽  
Stem Cell Differentiation ◽  
Myeloid Differentiation ◽  
Cycle Duration ◽  
Gene Circuits ◽  
Cell Cycles

Regulatory gene circuits with positive-feedback loops control stem cell differentiation, but several mechanisms can contribute to positive feedback. Here, we dissect feedback mechanisms through which the transcription factor PU.1 controls lymphoid and myeloid differentiation. Quantitative live-cell imaging revealed that developing B cells decrease PU.1 levels by reducing PU.1 transcription, whereas developing macrophages increase PU.1 levels by lengthening their cell cycles, which causes stable PU.1 accumulation. Exogenous PU.1 expression in progenitors increases endogenous PU.1 levels by inducing cell cycle lengthening, implying positive feedback between a regulatory factor and the cell cycle. Mathematical modeling showed that this cell cycle–coupled feedback architecture effectively stabilizes a slow-dividing differentiated state. These results show that cell cycle duration functions as an integral part of a positive autoregulatory circuit to control cell fate.

scholarly journals Context-dependent roles of YAP/TAZ in stem cell fates and cancer

2021 ◽  
Author(s):  
Lucy LeBlanc ◽  
Nereida Ramirez ◽  
Jonghwan Kim
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Control Cell ◽  
Substantial Portion ◽  
Cell Fates ◽  
Cell Fate Decisions ◽  
Cell Death Pathways ◽  
Multiple Context ◽  
Cancer Cell Survival ◽  
Context Dependent

AbstractHippo effectors YAP and TAZ control cell fate and survival through various mechanisms, including transcriptional regulation of key genes. However, much of this research has been marked by conflicting results, as well as controversy over whether YAP and TAZ are redundant. A substantial portion of the discordance stems from their contradictory roles in stem cell self-renewal vs. differentiation and cancer cell survival vs. apoptosis. In this review, we present an overview of the multiple context-dependent functions of YAP and TAZ in regulating cell fate decisions in stem cells and organoids, as well as their mechanisms of controlling programmed cell death pathways in cancer.

scholarly journals Functional Promiscuity of Gene Regulation by Serpentine Receptors in Dictyostelium discoideum

1998 ◽  
Vol 18 (10) ◽  
pp. 5744-5749 ◽  
Author(s):  
Irene Verkerke-Van Wijk ◽  
Ji-Yun Kim ◽  
Raymond Brandt ◽  
Peter N. Devreotes ◽  
Pauline Schaap
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Dictyostelium Discoideum ◽  
Developmental Regulation ◽  
Mutant Cell ◽  
Gene Induction ◽  
Specific Gene ◽  
Wild Type ◽  
Animal Development ◽  
Camp Stimulation

ABSTRACT Serpentine receptors such as smoothened and frizzled play important roles in cell fate determination during animal development. InDictyostelium discoideum, four serpentine cyclic AMP (cAMP) receptors (cARs) regulate expression of multiple classes of developmental genes. To understand their function, it is essential to know whether each cAR is coupled to a specific gene regulatory pathway or whether specificity results from the different developmental regulation of individual cARs. To distinguish between these possibilities, we measured gene induction in car1 car3 double mutant cell lines that express equal levels of either cAR1, cAR2, or cAR3 under a constitutive promoter. We found that all cARs efficiently mediate both aggregative gene induction by cAMP pulses and induction of postaggregative and prespore genes by persistent cAMP stimulation. Two exceptions to this functional promiscuity were observed. (i) Only cAR1 can mediate adenosine inhibition of cAMP-induced prespore gene expression, a phenomenon that was found earlier in wild-type cells. cAR1’s mediation of adenosine inhibition suggests that cAR1 normally mediates prespore gene induction. (ii) Only cAR2 allows entry into the prestalk pathway. Prestalk gene expression is induced by differentiation-inducing factor (DIF) but only after cells have been prestimulated with cAMP. We found that DIF-induced prestalk gene expression is 10 times higher in constitutive cAR2 expressors than in constitutive cAR1 or cAR3 expressors (which still have endogenous cAR2), suggesting that cAR2 mediates induction of DIF competence. Since in wild-type slugs cAR2 is expressed only in anterior cells, this could explain the so far puzzling observations that prestalk cells differentiate at the anterior region but that DIF levels are actually higher at the posterior region. After the initial induction of DIF competence, cAMP becomes a repressor of prestalk gene expression. This function can again be mediated by cAR1, cAR2, and cAR3.

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