scholarly journals Sensing of apoptotic cells through Axl causes lung basal cell proliferation in inflammatory diseases

2019 ◽  
Vol 216 (9) ◽  
pp. 2184-2201 ◽  
Author(s):  
Naoya Fujino ◽  
Oliver J. Brand ◽  
David J. Morgan ◽  
Toshifumi Fujimori ◽  
Aleksander M. Grabiec ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Division ◽  
Basal Cell ◽  
Inflammatory Diseases ◽  
Ciliated Cell ◽  
Apoptotic Cells ◽  
Basal Cells ◽  
Barrier Dysfunction ◽  
Cell Hyperplasia ◽  
Cell Cycle Reentry

Epithelial cell proliferation, division, and differentiation are critical for barrier repair following inflammation, but the initial trigger for this process is unknown. Here we define that sensing of apoptotic cells by the TAM receptor tyrosine kinase Axl is a critical indicator for tracheal basal cell expansion, cell cycle reentry, and symmetrical cell division. Furthermore, once the pool of tracheal basal cells has expanded, silencing of Axl is required for their differentiation. Genetic depletion of Axl triggers asymmetrical cell division, leading to epithelial differentiation and ciliated cell regeneration. This discovery has implications for conditions associated with epithelial barrier dysfunction, basal cell hyperplasia, and continued turnover of dying cells in patients with chronic inflammatory pulmonary diseases.

scholarly journals Focal neuroendocrine differentiation in prostatic gland carcinoma with basaloid pattern

2011 ◽  
Vol 68 (6) ◽  
pp. 515-518
Author(s):  
Jasmina Gligorijevic ◽  
Ljubinka Velickovic ◽  
Snezana Jancic ◽  
Zoran Radovanovic ◽  
Miljan Krstic ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Prostate Gland ◽  
Neuroendocrine Differentiation ◽  
Basal Cells ◽  
Cell Hyperplasia ◽  
Basal Cell Hyperplasia ◽  
Gland Carcinoma ◽  
Prostatic Gland

Introduction. Prostatic gland basal cell proliferations exhibit morphological continuum ranging from basal cell hyperplasia to basal cell carcinoma. In the following report, we described clinical features, morphological spectrum, neuroendocrine differentiation and histogenesis of prostatic gland basal cell carcinoma in our patient. Case report. Hematoxylineosin (HE), Alcian blu-periodic acid schiff (ABPAS) at pH 2.5 stained sections and the avidin-biotinperoxidase complex (ABC), were performed on prostate gland paraffin-embedded tissue. Monoclonal antibodies directed against cytokeratin (34?E12) which selectively stains basal cells, prostate specific antigen (PSA), chromogranine A, neuron-specific enolase (NSE), synaptophysin and CD56, were used. Basal cell proliferations exhibited a morphological continuum ranging from basal cell hyperplasia to prostatic gland carcinoma. In these prostatic lesions, positive reactivity was demonstrated for 34?E12 and CD56. These findings indicate that the basaloid cells of basal cell hyperplasia, florid basal cell hyperplasia, atypical basal cell hyperplasia and basal cell carcinoma are derived from basal cells of the normal prostate gland suggesting a continuum in the progression of hyperplasia to benign and then malignant neoplasia. The presence of CD56 protein in the discovered lesions may be related to their neuroendocrine differentiation. Conclusion. The fact, that our patient was well six years after the radical prostatectomy supports the belief of some authors that basal cell carcinoma represents a low grade carcinoma with an excellent prognosis.

scholarly journals Epidermal growth factor receptor activity is necessary for mouse basal cell proliferation

2014 ◽  
Vol 307 (10) ◽  
pp. L800-L810 ◽  
Author(s):  
Heather M. Brechbuhl ◽  
Bilan Li ◽  
Russell W. Smith ◽  
Susan D. Reynolds
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Basal Cell ◽  
Basal Cells ◽  
Epithelial Repair ◽  
Epidermal Growth ◽  
Proliferation In Vitro

ERB family receptors (EGFR, ERB-B2, ERB-B3, and ERB-B4) regulate epithelial cell function in many tissue types. In the human airway epithelium, changes in ERB receptor expression are associated with epithelial repair defects. However, the specific role(s) played by ERB receptors in repair have not been determined. We aimed to determine whether ERB receptors regulate proliferation of the tracheobronchial progenitor, the basal cell. Receptor tyrosine kinase arrays were used to evaluate ERB activity in normal and naphthalene (NA)-injured mouse trachea and in air-liquid interface cultures. Roles for epidermal growth factor (EGF), EGFR, and ERB-B2 in basal cell proliferation were evaluated in vitro. NA injury and transgenic expression of an EGFR-dominant negative (DN) receptor were used to evaluate roles for EGFR signaling in vivo. EGFR and ERB-B2 were active in normal and NA-injured trachea and were the only active ERB receptors detected in proliferating basal cells in vitro. EGF was necessary for basal cell proliferation in vitro. The EGFR inhibitor, AG1478, decreased proliferation by 99, and the Erb-B2 inhibitor, AG825, decreased proliferation by ∼66%. In vivo, EGFR-DN expression in basal cells significantly decreased basal cell proliferation after NA injury. EGF and EGFR are necessary for basal cell proliferation. The EGFR/EGFR homo- and the EGFR/ERB-B2 heterodimer account for ∼34 and 66%, respectively, of basal cell proliferation in vitro. Active EGFR is necessary for basal cell proliferation after NA injury. We conclude that EGFR activation is necessary for mouse basal cell proliferation and normal epithelial repair.

scholarly journals Transient Effects of Cyclophosphamide on Basal Cell Proliferation of Olfactory Epithelia

2020 ◽  
Vol 45 (7) ◽  
pp. 549-561
Author(s):  
Kyle B Joseph ◽  
Nora Awadallah ◽  
Eugene R Delay ◽  
Rona J Delay
Keyword(s):  
Cell Proliferation ◽  
Side Effects ◽  
Basal Cell ◽  
Vomeronasal Organ ◽  
Cell Renewal ◽  
Basal Cells ◽  
Transient Effects ◽  
Main Olfactory Epithelium ◽  
Immunohistochemical Markers ◽  
Horizontal Basal Cells

Abstract Cancer is often treated with broad-spectrum cytotoxic drugs that not only eradicate cancerous cells but also have detrimental side effects. One of these side effects, disruption of the olfactory system, impedes a patient’s ability to smell, perceive flavor, and ultimately may interfere with their nutritional intake and recovery from cancer. Recent studies reported that the chemotherapy drug, cyclophosphamide (CYP), can damage gustatory epithelia and disrupt cell proliferation in olfactory epithelia. In this study, we asked if CYP altered globose and horizontal basal cell proliferation in the murine main olfactory epithelium (MOE) and vomeronasal organ (VNO). We used antibodies for Ki67, a marker strictly associated with cell proliferation, and Keratin 5, a marker for the cytoskeleton of horizontal basal cells. Our results revealed a significant CYP-induced decrease in the number of proliferative cells in both epithelia, especially globose basal cells in the MOE, within the first 1–2 days postinjection. Recovery of cell renewal was apparent 6 days after injection. The immunohistochemical markers showed significantly higher levels of globose and horizontal basal cell proliferation in CYP-injected mice at 14 and 30 days postinjection compared with control mice. The prolonged proliferative activation of globose and horizontal basal cells suggests that, besides altering proliferation of olfactory epithelia, the epithelial substrate needed for successful cell renewal may be adversely affected by CYP.

scholarly journals Cadm1 regulates airway stem cell growth and differentiation via modulation of Stat3 activity

2016 ◽  
Author(s):  
Pooja Seedhar ◽  
Elizabeth K Sage ◽  
Sabari Vallath ◽  
Gabrielle Sturges ◽  
Adam Giangreco
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Differentiation ◽  
Basal Cell ◽  
Ciliated Cell ◽  
Basal Cells ◽  
Airway Injury ◽  
Cell Growth And Differentiation ◽  
Stat3 Signalling ◽  
Cell Adhesion Molecule 1

AbstractAirway homeostasis, repair, and regeneration are imperfectly understood processes involving the proliferation and differentiation of endogenous lung stem cells. Here, we establish that epithelial Cell adhesion molecule 1 (Cadm1) regulates the growth and differentiation of airway basal cells, previously identified as lung stem cells. Immunohistochemistry and gene expression analysis reveals that Cadm1 is broadly expressed throughout the murine tracheobronchial epithelium, exhibits transient downregulation concomitant with airway injury, and is subsequently restored during basal cell differentiation. Using Cadm1 null (KO) and keratin 14 (K14)-specific Cadm1 overexpressing transgenic mice, we demonstrate that maintaining Cadm1 expression reduces basal stem cell proliferation after tracheal polidocanol injury, whereas Cadm1 deletion causes increased ciliated cell differentiation and sustained downstream Stat3 signalling. Altogether, this study defines a previously uncharacterised role for Cadm1 in directing airway basal cell homeostasis and repair via modulation of Stat3 activity.

scholarly journals Single cell reconstruction of human basal cell diversity in normal and IPF lung

2020 ◽  
Author(s):  
Gianni Carraro ◽  
Apoorva Mulay ◽  
Changfu Yao ◽  
Takako Mizuno ◽  
Bindu Konda ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Single Cell ◽  
Lung Tissue ◽  
Basal Cell ◽  
Cell Subset ◽  
Cell Types ◽  
Molecular Signature ◽  
Basal Cells ◽  
Cell Hyperplasia

AbstractRationaleDeclining lung function in patients with interstitial lung disease is accompanied by epithelial remodeling and progressive scarring of the gas-exchange region. There is a need to better understand the contribution of basal cell hyperplasia and associated mucosecretory dysfunction to the development of idiopathic pulmonary fibrosis (IPF).ObjectivesWe sought to decipher the transcriptome of freshly isolated epithelial cells from normal and IPF lung to discern disease-dependent changes within basal stem cells.MethodsSingle cell RNA sequencing was used to map epithelial cell types of the normal and IPF human airway. Organoid and ALI cultures were used to investigate functional properties of basal cell subtypes.Measurements and Main ResultsWe found that basal cells included multipotent and secretory primed subsets in control adult lung tissue. Secretory primed basal cells include an overlapping molecular signature with basal cells obtained from distal lung tissue of IPF lungs. We confirmed that NOTCH2 maintains undifferentiated basal cells and restrict basal-to-ciliated differentiation, and present evidence that NOTCH3 functions to restrain secretory differentiation.ConclusionsBasal cells are dynamically regulated in disease and are specifically biased towards expansion of the secretory primed basal cell subset in idiopathic pulmonary fibrosis. Modulation of basal cell plasticity may represent a relevant target for therapeutic intervention in IPF.

scholarly journals Extracellular vesicles from human airway basal cells respond to cigarette smoke extract and affect vascular endothelial cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ashish Saxena ◽  
Matthew S. Walters ◽  
Jae-Hung Shieh ◽  
Ling-Bo Shen ◽  
Kazunori Gomi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cigarette Smoke ◽  
Extracellular Vesicles ◽  
Basal Cell ◽  
Mapk Signaling ◽  
Cigarette Smoke Extract ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Basal Cells ◽  
Human Airway

AbstractThe human airway epithelium lining the bronchial tree contains basal cells that proliferate, differentiate, and communicate with other components of their microenvironment. One method that cells use for intercellular communication involves the secretion of exosomes and other extracellular vesicles (EVs). We isolated exosome-enriched EVs that were produced from an immortalized human airway basal cell line (BCi-NS1.1) and found that their secretion is increased by exposure to cigarette smoke extract, suggesting that this stress stimulates release of EVs which could affect signaling to other cells. We have previously shown that primary human airway basal cells secrete vascular endothelial growth factor A (VEGFA) which can activate MAPK signaling cascades in endothelial cells via VEGF receptor–2 (VEGFR2). Here, we show that exposure of endothelial cells to exosome-enriched airway basal cell EVs promotes the survival of these cells and that this effect also involves VEGFR2 activation and is, at least in part, mediated by VEGFA present in the EVs. These observations demonstrate that EVs are involved in the intercellular signaling between airway basal cells and the endothelium which we previously reported. The downstream signaling pathways involved may be distinct and specific to the EVs, however, as increased phosphorylation of Akt, STAT3, p44/42 MAPK, and p38 MAPK was not seen following exposure of endothelial cells to airway basal cell EVs.

scholarly journals Cell fate clusters in ICM organoids arise from cell fate heredity and division: a modelling approach

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tim Liebisch ◽  
Armin Drusko ◽  
Biena Mathew ◽  
Ernst H. K. Stelzer ◽  
Sabine C. Fischer ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Division ◽  
Cell Fate ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Cell Lineage ◽  
Cell Fate Decision ◽  
Cell Fate Decisions ◽  
Chemical Signalling ◽  
Fate Decision

AbstractDuring the mammalian preimplantation phase, cells undergo two subsequent cell fate decisions. During the first decision, the trophectoderm and the inner cell mass are formed. Subsequently, the inner cell mass segregates into the epiblast and the primitive endoderm. Inner cell mass organoids represent an experimental model system, mimicking the second cell fate decision. It has been shown that cells of the same fate tend to cluster stronger than expected for random cell fate decisions. Three major processes are hypothesised to contribute to the cell fate arrangements: (1) chemical signalling; (2) cell sorting; and (3) cell proliferation. In order to quantify the influence of cell proliferation on the observed cell lineage type clustering, we developed an agent-based model accounting for mechanical cell–cell interaction, i.e. adhesion and repulsion, cell division, stochastic cell fate decision and cell fate heredity. The model supports the hypothesis that initial cell fate acquisition is a stochastically driven process, taking place in the early development of inner cell mass organoids. Further, we show that the observed neighbourhood structures can emerge solely due to cell fate heredity during cell division.

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