Transitional cells in the regenerating pancreas

Development ◽  
1994 ◽  
Vol 120 (7) ◽  
pp. 1873-1881 ◽  
Author(s):  
D. Gu ◽  
M.S. Lee ◽  
T. Krahl ◽  
N. Sarvetnick
Keyword(s):  
Islet Cell ◽  
Endocrine Cells ◽  
Cell Formation ◽  
Duct Cell ◽  
Cell Types ◽  
Carbonic Anhydrase Ii ◽  
Intermediate Cell ◽  
Transitional Cells ◽  
Intermediate Cells ◽  
Specific Pathway

We examined the spectrum of intermediate cell types in the regenerating pancreas as duct epithelial cells progressed through their differentiation pathway to become mature endocrine cells. The model used was transgenic mice in which the pancreatic islets continue to grow during adulthood, unlike normal mice whose islet cell formation ceases early in life. Because the intermediate cells migrated into islet-like clusters at specific locations, we propose a specific pathway for islet development. Endocrine cells are derived from duct cells co-expressing a duct cell antigen, carbonic anhydrase II (CA II) and an exocrine enzyme, amylase. The CA II/amylase cells become amylase/endocrine intermediate cells as they exited from their lumenal location. The abluminal amylase/endocrine cells continue to differentiate to multihormone-bearing young endocrine cells, which migrated to form clusters with other differentiating endocrine cells.

Intermediate Cells of the Pancreas

1972 ◽  
Vol 11 (2) ◽  
pp. 449-475 ◽  
Author(s):  
R. N. MELMED ◽  
CAROL J. BENITEZ ◽  
S. J. HOLT
Keyword(s):  
Guinea Pig ◽  
Endocrine Cells ◽  
Cell Types ◽  
Intermediate Cell ◽  
Normal Pancreas ◽  
Metabolic Demand ◽  
Widespread Occurrence ◽  
Morphological Criteria ◽  
Distinct Category ◽  
Intermediate Cells

The normal existence of cells in the pancreas with a structure intermediate between those of exocrine and endocrine cell types has long been a matter of dispute. The present study shows that, based upon morphological criteria, such intermediate cells are present in both the endocrine and exocrine tissues of the normal pancreas of the rat, guinea-pig, rhesus monkey, goat, chicken and frog. There is a tendency for intermediate cells to occur most frequently in the frog, where exocrine and endocrine cells are intermingled, and least frequently in higher species such as the rat, guinea-pig, monkey and goat where the endocrine cells are localized in discrete islets. Their occurrence in the chick appears to lie between these 2 extremes. The existence of intermediate cell types has been attributed to a ‘transformation’ of one form of specialized cell in the pancreas into another in response to a metabolic demand. However, the widespread occurrence of intermediate cells in the normal pancreas suggests that they represent, ab initio, a distinct category of cell, the existence of which poses interesting questions concerning the genetic control of their specialized functions and of developmental processes in the pancreas. Moreover, intermediate cells, such as acinar cells containing endocrine β-granules might serve as a source of insulin additional or alternative to that provided by cells that are wholly endocrine in character.

scholarly journals PD-1/PD-L1-negative tracheal mucoepidermoid carcinoma: A case report and systematic review of the literature

2021 ◽  
Author(s):  
Ying Ying Liu ◽  
Jian Guo ◽  
Ji Chen ◽  
Hai Xia Li ◽  
Zeng Tao Wang ◽  
...  
Keyword(s):  
Mucoepidermoid Carcinoma ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Cell Types ◽  
Intermediate Cell ◽  
Sleeve Lobectomy ◽  
Cell Lung Carcinoma ◽  
Segmental Bronchus ◽  
Intermediate Cells ◽  
Chinese Male

Abstract Background: Tracheal mucoepidermoid carcinoma is a rare form of non-small cell lung carcinoma and is defined as a tumor characterized by a combination of squamous, mucus-secreting, and intermediate cell types. This carcinoma is usually located in the lobar or segmental bronchus. Currently, surgery is the preferred treatment for this disease, which includes pneumonectomy, lobectomy, and sleeve lobectomy. Case presentation: A 50-year-old Chinese male presented with cough, shortness of breath and hemoptysis, and the effect of antibiotic therapy was not good. Subsequently, the airway occupied lesion was found by chest CT, and he was transferred to our hospital for surgical resection. Histologically, the tumor contained squamous epidermal cells, mucoepidermoid cells and intermediate cells. Immunohistochemistrically, the tumor cells were positive for p63, CK5/6, CK7 and Ki67. However, the tumor is generally negative for TTF-1 and neuroendocrine markers. The patient had no recurrence 15 months after the surgery.Conclusions: We report a rare case of mucoepidermoid carcinoma in the distal trachea in which the surgery was difficult and could not be performed like a traditional pulmonary resection. We first provide a comprehensive description of airway management and anesthesia intubation. After surgery, we reviewed the literature and found that PD-1/PD-L1 detection had never been reported in tracheal mucoepidermoid carcinoma. Therefore, we studied the PD-1/PD-L1 pathway in this patient, and the results were negative, which may indicate that potential adjuvant therapy with immune checkpoint inhibitors (ICIs) is not useful in this case.

scholarly journals PD-1/PD-L1-negative tracheal mucoepidermoid carcinoma: A case report and systematic review of the literature

2022 ◽  
pp. 260
Author(s):  
Keyword(s):  
Mucoepidermoid Carcinoma ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Cell Types ◽  
Intermediate Cell ◽  
Sleeve Lobectomy ◽  
Cell Lung Carcinoma ◽  
Segmental Bronchus ◽  
Intermediate Cells ◽  
Chinese Male

Background: Tracheal mucoepidermoid carcinoma is a rare form of non-small cell lung carcinoma and is defined as a tumor characterized by a combination of squamous, mucus-secreting, and intermediate cell types. This carcinoma is usually located in the lobar or segmental bronchus. Currently, surgery is the preferred treatment for this disease, which includes pneumonectomy, lobectomy, and sleeve lobectomy. Case presentation: A 50-year-old Chinese male presented with cough, shortness of breath and hemoptysis, and the effect of antibiotic therapy was not good. Subsequently, the airway occupied lesion was found by chest CT, and he was transferred to our hospital for surgical resection. Histologically, the tumor contained squamous epidermal cells, mucoepidermoid cells and intermediate cells. Immunohistochemistrically, the tumor cells were positive for p63, CK5/6, CK7 and Ki67. However, the tumor is generally negative for TTF-1 and neuroendocrine markers. The patient had no recurrence 15 months after the surgery. Conclusions: We report a rare case of mucoepidermoid carcinoma in the distal trachea in which the surgery was difficult and could not be performed like a traditional pulmonary resection. We first provide a comprehensive description of airway management and anesthesia intubation. After surgery, we reviewed the literature and found that PD-1/PD-L1 detection had never been reported in tracheal mucoepidermoid carcinoma. Therefore, we studied the PD-1/PD-L1 pathway in this patient, and the results were negative, which may indicate that potential adjuvant therapy with immune checkpoint inhibitors (ICIs) is not useful in this case.

Deficient epithelial-fibroblast heterocellular gap junction communication can be overcome by co-culture with an intermediate cell type but not by E-cadherin transgene expression

1998 ◽  
Vol 111 (23) ◽  
pp. 3529-3539 ◽  
Author(s):  
T.L. Woodward ◽  
M.A. Sia ◽  
O.W. Blaschuk ◽  
J.D. Turner ◽  
D.W. Laird
Keyword(s):  
Epithelial Cells ◽  
Gap Junction ◽  
Cell Lines ◽  
Intercellular Communication ◽  
Cell Types ◽  
Intermediate Cell ◽  
Cell Type ◽  
Gap Junction Intercellular Communication ◽  
Intermediate Cells ◽  
E Cadherin

Epithelial, fibroblast and intermediate cell lines were employed to examine the mechanism(s) essential for heterocellular gap junction intercellular communication in vitro. These cell lines were characterized extensively for cell type based on morphology, intermediate cytoskeletal proteins, cell adhesion molecules and their associated proteins, tight junction proteins as well as functional differentiation. All cell types expressed connexin43 and were dye-coupled in homocellular culture. Epithelial and intermediate cells or fibroblasts and intermediate cells readily assembled heterocellular connexin43-positive gap junction plaques when co-cultured, while gap junction plaques in mixed cultures of epithelial cells and fibroblasts were rare. Dye microinjection studies were used to show that there was little gap junction intercellular communication between epithelial cells and fibroblasts. However, intermediate cells were able to communicate with epithelial cells and, to a lesser extent, fibroblasts and could transfer dye to both epithelial cells and fibroblasts when all three cell types were cultured together. Fibroblasts that were stably transfected with a cDNA encoding E-cadherin had a greater tendency to aggregate and exhibited a more epithelial-like phenotype but heterocellular gap junction intercellular communication with epithelial cells, which endogenously express E-cadherin, was not enhanced. These results suggest that mutual expression of E-cadherin is insufficient to stimulate gap junction formation between epithelial cells and fibroblasts. Moreover, our results also demonstrate that communication gaps between epithelial cells and fibroblasts can be bridged by intermediate cells, a process that may be important in mammary gland development, growth, differentiation and cancer.

scholarly journals Semisoft clustering of single-cell data

2018 ◽  
Vol 116 (2) ◽  
pp. 466-471 ◽  
Author(s):  
Lingxue Zhu ◽  
Jing Lei ◽  
Lambertus Klei ◽  
Bernie Devlin ◽  
Kathryn Roeder
Keyword(s):  
Gene Expression ◽  
Developmental Trajectories ◽  
Clustering Algorithms ◽  
Fetal Brain ◽  
Cell Types ◽  
Intermediate Cell ◽  
Pure Cell ◽  
Continuous Mixture ◽  
Transitional Cells ◽  
Membership Matrix

Motivated by the dynamics of development, in which cells of recognizable types, or pure cell types, transition into other types over time, we propose a method of semisoft clustering that can classify both pure and intermediate cell types from data on gene expression from individual cells. Called semisoft clustering with pure cells (SOUP), this algorithm reveals the clustering structure for both pure cells and transitional cells with soft memberships. SOUP involves a two-step process: Identify the set of pure cells and then estimate a membership matrix. To find pure cells, SOUP uses the special block structure in the expression similarity matrix. Once pure cells are identified, they provide the key information from which the membership matrix can be computed. By modeling cells as a continuous mixture of K discrete types we obtain more parsimonious results than obtained with standard clustering algorithms. Moreover, using soft membership estimates of cell type cluster centers leads to better estimates of developmental trajectories. The strong performance of SOUP is documented via simulation studies, which show its robustness to violations of modeling assumptions. The advantages of SOUP are illustrated by analyses of two independent datasets of gene expression from a large number of cells from fetal brain.

scholarly journals Loss of Adam10 disrupts ion transport in immortalised kidney collecting duct cells

Function ◽  
2021 ◽  
Author(s):  
Adrienne Assmus ◽  
Linda Mullins ◽  
Mairi Ward ◽  
Ross Dobie ◽  
Robert Hunter ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Notch Pathway ◽  
Cell Types ◽  
Intermediate Cell ◽  
Cortical Collecting Duct ◽  
Cell Type ◽  
Intercalated Cell ◽  
Collecting Duct Cells ◽  
Intermediate Cells ◽  
Diffuse Distribution

Abstract The kidney cortical collecting duct (CCD) comprises of principal cells (PC), intercalated cells (IC) and the recently discovered intermediate cell type. Kidney pathology in a mouse model of the syndrome of apparent aldosterone excess (SAME) revealed plasticity of the cortical collecting duct (CCD), with altered principal cell (PC): intermediate cell: intercalated cell (IC) ratio. The self-immortalized mouse CCD cell line, mCCDcl1, shows functional characteristics of PCs but displays a range of cell types, including intermediate cells, making it ideal to study plasticity. We knocked out Adam10, a key component of the Notch pathway, in mCCDcl1 cells, using CRISPR-Cas9 technology, and isolated independent clones, which exhibited severely affected sodium transport capacity and loss of aldosterone response. Single-cell RNA sequencing revealed significantly reduced expression of major PC-specific markers, such as Scnn1g (γ-ENaC) and Hsd11b2 (11ßHSD2), but no significant changes in transcription of components of the Notch pathway were observed. Immunostaining in the knockout clone confirmed the decrease in expression of γ-ENaC and importantly, showed an altered, diffuse distribution of PC and IC markers, suggesting altered trafficking in the Adam10 knockout clone as an explanation for the loss of polarisation.

Epithelial cell proliferation and islet neogenesis in IFN-g transgenic mice

Development ◽  
1993 ◽  
Vol 118 (1) ◽  
pp. 33-46 ◽  
Author(s):  
D. Gu ◽  
N. Sarvetnick
Keyword(s):  
Transgenic Mice ◽  
Islet Cell ◽  
Endocrine Cells ◽  
Islet Cells ◽  
Cell Types ◽  
Model System ◽  
Epithelial Cell Proliferation ◽  
Islet Neogenesis ◽  
Islet Development ◽  
Duct Cells

We have identified a model system for the study of pancreatic islet development and regeneration in transgenic mice bearing the interferon-gamma (IFN-g) gene expressed in the pancreatic islets. Previous studies showed that the locally produced IFN-g causes lymphocyte infiltration and islet cell destruction. Here we demonstrate that new islet cells are formed continuously from duct cells as evidenced by (1) the dramatic proliferation of duct cells, (2) the appearance of primitive cells and (3) their subsequent differentiation to endocrine cells. The IFN-g induced islet neogenesis is similar to embryonic islet morphogenesis and offers a model system for studying factors modulating islet development. Additionally, the duct cells occasionally transdifferentiate to gastrointestinal-like cell types and hepatocytes. These results underscore the lymphokine's ability to initiate a complex ‘transdifferentiation’ pathway, providing a window for understanding lineage interrelationships within a terminally differentiated structure.

scholarly journals Induction and origin of hepatocytes in rat pancreas.

1984 ◽  
Vol 98 (6) ◽  
pp. 2082-2090 ◽  
Author(s):  
J K Reddy ◽  
M S Rao ◽  
S A Qureshi ◽  
M K Reddy ◽  
D G Scarpelli ◽  
...  
Keyword(s):  
Endocrine Cells ◽  
Secretory Granules ◽  
Volume Density ◽  
Peroxisome Proliferator ◽  
Rat Hepatocyte ◽  
Transitional State ◽  
Transitional Cells ◽  
Acinar Tissue ◽  
Intermediate Cells ◽  
Pancreatic Hepatocytes

2-[4(2,2- Dichlorocyclopropyl )phenoxy]2-methyl propionic acid (ciprofibrate), a peroxisome proliferator , induced hepatocytes in the pancreas of adult male F-344 rats when added to their diet at a dosage of 10 mg/kg body weight for 60-72 wk. These cells are morphologically indistinguishable from hepatic hepatocytes and were usually localized adjacent to islets of Langerhans with extensions into surrounding acinar tissue. A significant increase in the volume density of peroxisomes, together with immunochemically detectable amounts of two peroxisome-associated enzymes, was observed in pancreas with hepatocytes of rats maintained on ciprofibrate. Uricase-containing crystalloid nucleoids, specific for rat hepatocyte peroxisomes, were present in pancreatic hepatocytes. These structures facilitated the identification of cells with hybrid cytoplasmic features characteristic of pancreatic acinar and endocrine cells and hepatocytes. Such cells are presumed to represent a transitional state in which pancreas specific genes are being repressed while liver specific ones are simultaneously expressed. The presence of exocrine and/or endocrine secretory granules in transitional cells indicates that acinar/intermediate cells represent the precursor cell from which pancreatic hepatocytes are derived.

Expression of peptide YY in all four islet cell types in the developing mouse pancreas suggests a common peptide YY-producing progenitor

Development ◽  
1994 ◽  
Vol 120 (2) ◽  
pp. 245-252 ◽  
Author(s):  
B.H. Upchurch ◽  
G.W. Aponte ◽  
A.B. Leiter
Keyword(s):  
Transgenic Mice ◽  
Pancreatic Polypeptide ◽  
Islet Cell ◽  
Endocrine Cells ◽  
Peptide Yy ◽  
Cell Types ◽  
T Antigen ◽  
Cell Lineages ◽  
Pancreatic Polypeptide Cells ◽  
Islet Cell Types

The islets of Langerhans contain four distinct endocrine cell types producing the hormones glucagon, insulin, somatostatin and pancreatic polypeptide. These cell lineages are thought to arise from a common, multipotential progenitor cell whose identity has not been well established. The pancreatic and intestinal hormone, peptide YY, has been previously identified in glucagon-producing cells in islets; however, transgenic mice expressing Simian Virus 40 large T antigen under the control of the peptide YY gene expressed the oncoprotein in beta, delta and pancreatic polypeptide cells, and occasionally developed insulinomas, suggesting relationships between peptide YY-producing cells and several islet cell lineages. The four established pancreatic islet cell types were examined for coexpression of peptide YY in islets of normal and transgenic mice throughout development. Peptide YY immunoreactivity was identified in the earliest endocrine cells in the fetal pancreas and was coexpressed in each islet cell type during development. Peptide YY showed a high degree of co-localization with glucagon- and insulin-producing cells in early pancreatic development, but by adulthood, peptide YY was expressed in less than half of the alpha cells and was no longer expressed in beta cells. Peptide YY was also coexpressed with somatostatin and pancreatic polypeptide when these cell types first appeared, but most delta and pancreatic polypeptide cells continued to express peptide YY throughout development. The use of conditions that distinguish peptide YY from the related peptides, pancreatic polypeptide and neuropeptide Y, as well as the ability of the peptide YY gene to direct expression of a reporter gene in islets of transgenic mice, establishes expression of peptide YY in the earliest pancreatic endocrine cells.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Characterization of the inositol 1,4,5-trisphosphate-induced calcium release from permeabilized endocrine cells and its inhibition by decavanadate and p-hydroxymercuribenzoate

1989 ◽  
Vol 262 (1) ◽  
pp. 83-89 ◽  
Author(s):  
K J Föhr ◽  
J Scott ◽  
G Ahnert-Hilger ◽  
M Gratzl
Keyword(s):  
Endocrine Cells ◽  
Calcium Release ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Maximal Effect ◽  
Thiol Compounds ◽  
Inositol 1,4,5 Trisphosphate ◽  
Dependent Inhibition ◽  
Pheochromocytoma Pc12 ◽  
First Time

The inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ compartment of endocrine cells was studied with alpha-toxin- and digitonin-permeabilized rat insulinoma (RINA2) and rat pheochromocytoma (PC12) cells. The Ca2+ uptake was ATP-dependent, and submicromolar concentrations of IP3 specifically released the stored Ca2+. Half-maximal Ca2+ release was observed with 0.25-0.5 mumol of IP3/l, and the amount of Ca2+ released due to IP3 could be enhanced by additional loading of the Ca2+ compartment. Consecutive additions of the same concentration of IP3 for 1-2 h always released the same amount of Ca2+ without desensitization, providing an ideal basis to further characterize the IP3-induced Ca2+ release. Here we describe for the first time a reversible inhibitory effect of decavanadate on the IP3-induced Ca2+ release. Among the vanadium species tested (decavanadate, oligovanadate and monovanadate), only decavanadate was inhibitory, with a half-maximal effect at 5 mumol/l in both cell types. The effect of decavanadate could be overcome by increasing the amount of sequestered Ca2+ or added IP3. Decavanadate did not affect the ATP-driven Ca2+ uptake but oligovanadate was inhibitory on Ca2+ uptake. p-Hydroxymercuribenzoate (pHMB) at concentrations between 10 and 30 mumol/l also inhibited the Ca2+ release due to IP3. Thiol compounds such as dithiothreitol (DTT; 1 mmol/l) added before pHMB removed all its inhibitory effect on the IP3-induced Ca2+ release, whereas the inhibition caused by decavanadate was unaffected by DTT. Thus, the decavanadate-dependent inhibition functions by a distinctly different mechanism than pHMB and could serve as a specific tool to analyse various aspects of the IP3-induced Ca2+ release within endocrine cells.

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