scholarly journals Expression of a homologously recombined erythopoietin-SV40 T antigen fusion gene in mouse liver: evidence for erythropoietin production by Ito cells

Blood ◽  
1994 ◽  
Vol 84 (6) ◽  
pp. 1823-1830 ◽  
Author(s):  
PH Maxwell ◽  
DJ Ferguson ◽  
MK Osmond ◽  
CW Pugh ◽  
A Heryet ◽  
...  

Abstract We have obtained transgenic mice in which an erythropoietin-SV40 virus T antigen fusion gene is homologously recombined into the native Epo locus. This gene is expressed in a tissue-specific manner closely resembling that of the native Epo gene. Immunohistochemical detection of SV40 T antigen has been used to characterize the hepatic cell populations expressing the transgene. In mice stimulated by anaemia or hypobaric hypoxia, SV40 T antigen was demonstrated in two liver cell populations: a subset of hepatocytes and a nonparenchymal cell type. Immunohistochemical and ultrastructural characterization of these cells by light and electron microscopy showed the nonparenchymal cell type to be the Ito cells, which lie in a persinusoidal position within the space of Disse. We therefore conclude that Ito cells are the nonhepatocytic source of liver Epo production. These cells show many similarities to the Epo-producing fibroblastoid interstitial cells of the kidney.

Blood ◽  
1994 ◽  
Vol 84 (6) ◽  
pp. 1823-1830 ◽  
Author(s):  
PH Maxwell ◽  
DJ Ferguson ◽  
MK Osmond ◽  
CW Pugh ◽  
A Heryet ◽  
...  

We have obtained transgenic mice in which an erythropoietin-SV40 virus T antigen fusion gene is homologously recombined into the native Epo locus. This gene is expressed in a tissue-specific manner closely resembling that of the native Epo gene. Immunohistochemical detection of SV40 T antigen has been used to characterize the hepatic cell populations expressing the transgene. In mice stimulated by anaemia or hypobaric hypoxia, SV40 T antigen was demonstrated in two liver cell populations: a subset of hepatocytes and a nonparenchymal cell type. Immunohistochemical and ultrastructural characterization of these cells by light and electron microscopy showed the nonparenchymal cell type to be the Ito cells, which lie in a persinusoidal position within the space of Disse. We therefore conclude that Ito cells are the nonhepatocytic source of liver Epo production. These cells show many similarities to the Epo-producing fibroblastoid interstitial cells of the kidney.


1993 ◽  
Vol 30 (2) ◽  
pp. 111-118 ◽  
Author(s):  
J. M. Cullen ◽  
E. P. Sandgren ◽  
R. L. Brinster ◽  
R. R. Maronpot

The development of hepatic neoplasms was histologically characterized in transgenic mice that expressed an albumin enhancer-promotor/SV40 T-antigen fusion gene. At least five transgenic and three control mice were examined at monthly intervals over a 3-month period. At 1 month of age, five transgenic mice (two male, three female) and three controls (one male, two female) were examined. Five transgenic mice (two male, three female) and three controls (one male, two female) were examined at 2 months of age. Fourteen transgenic mice (12 male, two female) and three controls (two male, one female) were examined at 3 months of age. At 1 month of age, liver-to-body weight ratios of transgenic mice were increased nearly twofold as compared with controls. Histologically, livers from transgenic mice were characterized by dysplastic hepatocytes with marked variation in nucleus and cell size. At 2 months of age, livers from transgenic mice were 2.5 times larger than control livers and contained numerous 1–5-mm cystic spaces. Transgenic livers also contained multiple eosinophilic, basophilic, and clear foci, as well as cystic, hyperplastic bile ducts and biliary adenomas. At 3 months of age, transgenic livers were enlarged over eightfold as compared with controls and contained numerous cysts and solid masses up to 2 cm in diameter. Trabecular, glandular, and anaplastic hepatocellular carcinomas, as well as benign and malignant biliary neoplasms, were diagnosed. No metastasis was observed. Subcutaneous trabecular hepatocellular carcinomas developed in two of three syngeneic mice that had received transplants of a solid hepatic neoplasm, confirming the neoplastic behavior of these tumors. These experiments, in which viral oncogene expression is targeted to all hepatocytes, support the multistage hypothesis of tumor development and illustrate the similarities in morphologic response of liver to a variety of carcinogenic insults.


2021 ◽  
Author(s):  
Mariia Bilous ◽  
Loc Tran ◽  
Chiara Cianciaruso ◽  
Santiago J Carmona ◽  
Mikael J Pittet ◽  
...  

Single-cell RNA sequencing (scRNA-seq) technologies offer unique opportunities for exploring heterogeneous cell populations. However, in-depth single-cell transcriptomic characterization of complex tissues often requires profiling tens to hundreds of thousands of cells. Such large numbers of cells represent an important hurdle for downstream analyses, interpretation and visualization. Here we develop a network-based coarse-graining framework where highly similar cells are merged into super-cells. We demonstrate that super-cells not only preserve but often improve the results of downstream analyses including visualization, clustering, differential expression, cell type annotation, gene correlation, imputation, RNA velocity and data integration. By capitalizing on the redundancy inherent to scRNA-seq data, super-cells significantly facilitate and accelerate the construction and interpretation of single-cell atlases, as demonstrated by the integration of 1.46 million cells from COVID-19 patients in less than two hours on a standard desktop.


1992 ◽  
Vol 28 (7-8) ◽  
pp. 461-464 ◽  
Author(s):  
Joan H. Schiller ◽  
Chinghai Kao ◽  
Gerard Bittner ◽  
Chuck Harris ◽  
Terry D. Oberley ◽  
...  

2010 ◽  
Vol 16 (6) ◽  
pp. 688-698 ◽  
Author(s):  
Alexandre Lobo-da-Cunha ◽  
Elsa Oliveira ◽  
Íris Ferreira ◽  
Rita Coelho ◽  
Gonçalo Calado

AbstractThe posterior esophagus of Bulla striata, running from the gizzard to the stomach, was investigated with light and electron microscopy to obtain new data for a comparative analysis of the digestive system in cephalaspidean opisthobranchs. In this species, the posterior esophagus can be divided into two regions. In the first, the epithelium is formed by columnar cells with apical microvilli embedded in a cuticle. Many epithelial and subepithelial secretory cells are present in this region. In both, electron-lucent secretory vesicles containing filaments and a peripheral round mass of secretory material fill the cytoplasm. These acid mucus-secreting cells may also contain a few dense secretory vesicles. In the second part of the posterior esophagus, the cuticle is absent and the epithelium is ciliated. In this region, epithelial cells may contain larger lipid droplets and glycogen reserves. Subepithelial secretory cells are not present, and in epithelial secretory cells the number of dense vesicles increases, but most secretory cells still contain some electron-lucent vesicles. These cells secrete a mixture of proteins and acid polysaccharides and should be considered seromucous. The secretory cells of the posterior esophagus are significantly different from those previously reported in the anterior esophagus of this herbivorous species.


Cell ◽  
1974 ◽  
Vol 3 (1) ◽  
pp. 65-70 ◽  
Author(s):  
I.Craig Henderson ◽  
David M. Livingston

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