scholarly journals Cell-lineage specificity of primary cilia during epididymis post-natal development

2018 ◽  
Author(s):  
Agathe Bernet ◽  
Alexandre Bastien ◽  
Denis Soulet ◽  
Olivia Jerczynski ◽  
Christian Roy ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Hedgehog Signaling ◽  
Primary Cilia ◽  
Cell Lineage ◽  
Basal Cells ◽  
Myoid Cells ◽  
Apical Pole ◽  
Lineage Specificity ◽  
Spatio Temporal ◽  
Temporal Localization

AbstractPrimary cilia are sensory organelles that orchestrate major signaling pathways during organ development and homeostasis. By using a double Arl13b/mCherry-Cetn2/GFP transgenic mouse model, we characterized the spatio-temporal localization of primary cilia in the epididymis, from birth to adulthood. We report here a constitutive localisation of primary cilia in peritubular myoid cells and a dynamic profiling in differentiated epithelial cells throughout post-natal development. While primary cilia are present at the apical pole of the undifferentiated epithelial cells from birth to puberty, they are absent from the apical pole of the epithelium in adults, where they appear exclusively associated with cytokeratin 5-positive basal cells. Exogenous labeling of primary cilia marker Arl13b and IFT88 confirmed the cell lineage specific localization of primary cilia in basal cells and myoid cells in human epididymides. From whole epididymis tissues and serum-free cultures of DC2 murine epididymal principal cell lines we determined that primary cilia from the epididymis are associated with the polycystic kidney disease-related proteins polycystin 1 (PC1) and polycystin 2 (PC2), and Gli3 Hedgehog signaling transcription factor. Thus, our findings unveil the existence of primary cilia sensory organelles, which have the potential to mediate mechano/ chemo-signaling events in the epididymis.

scholarly journals Cell-lineage specificity of primary cilia during postnatal epididymal development

2018 ◽  
Vol 33 (10) ◽  
pp. 1829-1838 ◽  
Author(s):  
Agathe Bernet ◽  
Alexandre Bastien ◽  
Denis Soulet ◽  
Olivia Jerczynski ◽  
Christian Roy ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Cell Lineage ◽  
Lineage Specificity

scholarly journals Acid Dentin Lysates Increase Amelotin Expression in Oral Epithelial Cells and Gingival Fibroblasts

2021 ◽  
Vol 11 (12) ◽  
pp. 5394
Author(s):  
Jila Nasirzade ◽  
Zahra Kargarpour ◽  
Layla Panahipour ◽  
Reinhard Gruber
Keyword(s):  
Epithelial Cells ◽  
Oral Cavity ◽  
Calcium Binding ◽  
Transforming Growth Factor ◽  
Cell Lineage ◽  
Bone Morphogenetic Protein 2 ◽  
Tooth Surface ◽  
Enamel Matrix Derivative ◽  
Gingival Fibroblasts ◽  
Smad 3

Amelotin (AMTN) is a secretory calcium-binding phosphoprotein controlling the adhesion of epithelial cells to the tooth surface, forming a protective seal against the oral cavity. It can be proposed that signals released upon dentinolysis increase AMTN expression in periodontal cells, thereby helping to preserve the protective seal. Support for this assumption comes from our RNA sequencing approach showing that gingival fibroblasts exposed to acid dentin lysates (ADL) greatly increased AMTN expression. In the present study, we confirm that acid dentin lysates significantly increase AMTN in gingival fibroblasts and extend this observation towards the epithelial cell lineage by use of the HSC2 oral squamous and TR146 buccal carcinoma cell lines. AMTN immunostaining revealed an intensive signal in the nucleus of HSC2 cells exposed to acid dentin lysates. Acid dentin lysates mediate their effect via the transforming growth factor (TGF)-β type 1 receptor kinase as the antagonist SB431542 abolished the expression of AMTN in the epithelial cells and fibroblasts. Similar to what is known for fibroblasts, acid dentin lysate increased Smad-3 phosphorylation in HSC2 cells. HSC2 cells also respond to the AMTN-stimulating activity of the dentin lysate when adsorbed to gelatin. When simulating regenerative approaches, enamel matrix derivative, TGF-β1, and bone morphogenetic protein-2 also caused a robust increase in SB431542-dependent AMTN expression in HSC2. Taken together, we show here that acid dentin lysate uses the TGF-β-depended signaling pathway to support the AMTN expression in epithelial cells, possibly helping in maintaining the protective seal against the oral cavity.

scholarly journals Motional dynamics of single Patched1 molecules in cilia are controlled by Hedgehog and cholesterol

2019 ◽  
Vol 116 (12) ◽  
pp. 5550-5557 ◽  
Author(s):  
Lucien E. Weiss ◽  
Ljiljana Milenkovic ◽  
Joshua Yoon ◽  
Tim Stearns ◽  
W. E. Moerner
Keyword(s):  
Single Molecule ◽  
Hedgehog Signaling ◽  
Primary Cilia ◽  
Transmembrane Protein ◽  
Cellular Level ◽  
Live Cells ◽  
Cholesterol Depletion ◽  
Motional Dynamics ◽  
Directional Transport ◽  
Bulk Behavior

The Hedgehog-signaling pathway is an important target in cancer research and regenerative medicine; yet, on the cellular level, many steps are still poorly understood. Extensive studies of the bulk behavior of the key proteins in the pathway established that during signal transduction they dynamically localize in primary cilia, antenna-like solitary organelles present on most cells. The secreted Hedgehog ligand Sonic Hedgehog (SHH) binds to its receptor Patched1 (PTCH1) in primary cilia, causing its inactivation and delocalization from cilia. At the same time, the transmembrane protein Smoothened (SMO) is released of its inhibition by PTCH1 and accumulates in cilia. We used advanced, single molecule-based microscopy to investigate these processes in live cells. As previously observed for SMO, PTCH1 molecules in cilia predominantly move by diffusion and less frequently by directional transport, and spend a fraction of time confined. After treatment with SHH we observed two major changes in the motional dynamics of PTCH1 in cilia. First, PTCH1 molecules spend more time as confined, and less time freely diffusing. This result could be mimicked by a depletion of cholesterol from cells. Second, after treatment with SHH, but not after cholesterol depletion, the molecules that remain in the diffusive state showed a significant increase in the diffusion coefficient. Therefore, PTCH1 inactivation by SHH changes the diffusive motion of PTCH1, possibly by modifying the membrane microenvironment in which PTCH1 resides.

scholarly journals Activation of Cilia-Independent Hedgehog/GLI1 Signaling as a Novel Concept for Neuroblastoma Therapy

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1908
Author(s):  
Anke Koeniger ◽  
Anna Brichkina ◽  
Iris Nee ◽  
Lukas Dempwolff ◽  
Anna Hupfer ◽  
...  
Keyword(s):  
Hedgehog Signaling ◽  
Primary Cilia ◽  
Survival Rates ◽  
Genetic Alterations ◽  
Novel Therapy ◽  
Therapeutic Concept ◽  
Pathway Activation ◽  
Starting Point ◽  
Novel Concept ◽  
Neural Crest Differentiation

Although being rare in absolute numbers, neuroblastoma (NB) represents the most frequent solid tumor in infants and young children. Therapy options and prognosis are comparably good for NB patients except for the high risk stage 4 class. Particularly in adolescent patients with certain genetic alterations, 5-year survival rates can drop below 30%, necessitating the development of novel therapy approaches. The developmentally important Hedgehog (Hh) pathway is involved in neural crest differentiation, the cell type being causal in the etiology of NB. However, and in contrast to its function in some other cancer types, Hedgehog signaling and its transcription factor GLI1 exert tumor-suppressive functions in NB, rendering GLI1 an interesting new candidate for anti-NB therapy. Unfortunately, the therapeutic concept of pharmacological Hh/GLI1 pathway activation is difficult to implement as NB cells have lost primary cilia, essential organelles for Hh perception and activation. In order to bypass this bottleneck, we have identified a GLI1-activating small molecule which stimulates endogenous GLI1 production without the need for upstream Hh pathway elements such as Smoothened or primary cilia. This isoxazole compound potently abrogates NB cell proliferation and might serve as a starting point for the development of a novel class of NB-suppressive molecules.

Deep Learning for Spatio-Temporal Localization of Temporomandibular Joint in Ultrasound Videos

2021 ◽  
Author(s):  
Kristina Belikova ◽  
Aleksandra Zailer ◽  
Svetlana V. Tekucheva ◽  
Sergey N. Ermoljev ◽  
Dmitry V. Dylov
Keyword(s):  
Deep Learning ◽  
Temporomandibular Joint ◽  
Spatio Temporal ◽  
Temporal Localization

scholarly journals The cell cycle state defines TACC3 as a regulator gene in glioblastoma

2020 ◽  
Author(s):  
Holly Briggs ◽  
Euan S. Polson ◽  
Bronwyn K. Irving ◽  
Alexandre Zougman ◽  
Ryan K. Mathew ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gene Networks ◽  
Coiled Coil ◽  
Cell Lineage ◽  
Progression Free Survival ◽  
Low Grade ◽  
Loss Of Function ◽  
Feature Maps ◽  
Clinical Databases ◽  
Lineage Specificity

AbstractOverexpression and mitosis-promoting roles of Transforming acidic coiled-coil containing protein 3 (TACC3) are well-established in many cancers, including glioblastoma (GBM). However, the effector gene networks downstream of TACC3 remain poorly defined, partly due to an incomplete understanding of TACC3 cell lineage specificity and its dynamic role during the cell cycle. Here, we use a patient-derived GBM model to report that TACC3 predominantly resides in the GBM cell cytoplasm, while engaging in gene regulation temporally as defined by the cell cycle state. TACC3 loss-of-function, cell cycle stage-specific transcriptomics, and unsupervised self-organizing feature maps revealed pathways (including Hedgehog signalling) and individual genes (including HOTAIR) that exhibited anticorrelated expression phenotypes across interphase and mitosis. Furthermore, this approach identified a set of 22 TACC3-dependent transcripts in publicly-available clinical databases that predicted poor overall and progression-free survival in 162 GBM and 514 low-grade glioma patient samples. These findings uncover TACC3-dependent genes as a function of TACC3 cell cycle oscillation, which is important for TACC3-targeting strategies, and for predicting poor outcomes in brain cancer patients.

scholarly journals The expression and localization of V-ATPase and cytokeratin 5 during postnatal development of the pig epididymis

2020 ◽  
Vol 33 (7) ◽  
pp. 1077-1086 ◽  
Author(s):  
Yun-Jae Park ◽  
Ji-Hyuk Kim ◽  
Hack-Youn Kim ◽  
Hee-Bok Park ◽  
Juhui Choe ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Expression Patterns ◽  
Basal Cells ◽  
Cell Type ◽  
Clear Cells ◽  
Specific Distribution ◽  
Cytokeratin 5 ◽  
Cell Type Specific ◽  
Immunofluorescence Labeling ◽  
And Storage

Objective: We examined the localization and expression of H<sup>+ pumping vacuolar ATPase (V-ATPase) and cytokeratin 5 (KRT5) in the epididymis of pigs, expressed in clear and basal cells, respectively, during postnatal development.Methods: Epididymides were obtained from pigs at 1, 7, 21, 60, 120, and 180 days of age; we observed the localization and expression patterns of V-ATPase and KRT5 in the different regions of these organs, namely, the caput, corpus, and cauda. The differentiation of epididymal epithelial cells was determined by immunofluorescence labeling using cell-type-specific markers and observed using confocal microscopy.Results: At postnatal day 5 (PND5), the localization of clear cells commenced migration from the cauda toward the caput. Although at PND120, goblet-shaped clear cells were detected along the entire length of the epididymis, those labeled for V-ATPase had disappeared from the corpus to cauda and were maintained only in the caput epididymis in adult pigs. In contrast, whereas basal cells labeled for KRT5 were only present in the vas deferens at birth, they were detected in all regions of the epididymis at PND60. These cells were localized at the base of the epithelium; however, no basal cells characterized by luminally extending cell projections were observed in any of the adult epididymides examined.Conclusion: The differentiation of clear and basal cells progressively initiates in a retrograde manner from the cauda to the caput epididymis. The cell-type-specific distribution and localization of the epithelial cells play important roles in establishing a unique luminal environment for sperm maturation and storage in the pig epididymis.

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