scholarly journals Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver

iScience ◽  
2021 ◽  
pp. 103233
Author(s):  
Qi Su ◽  
Sun Y. Kim ◽  
Funmi Adewale ◽  
Ye Zhou ◽  
Christina Aldler ◽  
...  
2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi205-vi206
Author(s):  
Roland Kälin ◽  
Linzhi Cai ◽  
Yuping Li ◽  
Ines Hellmann ◽  
Rainer Glass

Abstract Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor-parenchymal cells may promote specific phases of disease-progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Strikingly, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell-population, by conditional Sox2-knockout, drastically reduced glioblastoma-vascularization and -size. TAMEP manipulation profoundly altered vessel function and strongly attenuated the blood-tumor barrier. Hence, our data indicate TAMEP and their progenitors as new targets for glioblastoma therapy.


2006 ◽  
Vol 84 (2) ◽  
pp. 250-256 ◽  
Author(s):  
Jany Lapointe ◽  
To Quyen Truong ◽  
Louise Falstrault ◽  
Louise Brissette

The aim of this study was to quantify the abilities of mouse liver parenchymal and nonparenchymal cells with respect to (i) cholesteryl ester (CE) selective uptake from low-density lipoproteins (LDL), oxidized LDL (OxLDL), and high-density lipoprotein (HDL); and (ii) their free cholesterol efflux to HDL. The preparations of cells were incubated with lipoproteins labelled either in protein with iodine-125 or in CE with 3H-cholesterol oleate, and lipoprotein-protein and lipoprotein-CE associations were measured. The associations of LDL-protein and LDL-CE with nonparenchymal cells were 5- and 2-fold greater, respectively, than with parenchymal cells. However, in terms of CE-selective uptake (CE association minus protein association) both types of cell were equivalent. Similar results were obtained with OxLDL, but both types of cell showed higher abilities in OxLDL-CE than in LDL-CE selective uptake (on average by 3.4-fold). The association of HDL-protein with nonparenchymal cells was 3× that with parenchymal cells; however, nonparenchymal cells associated 45% less HDL-CE. Contrary to parenchymal cells, nonparenchymal cells did not show HDL-CE selective uptake activity. Thus parenchymal cells selectively take CE from the 3 types of lipoproteins, whereas nonparenchymal cells exert this function only on LDL and OxLDL. Efflux was 3.5-fold more important in nonparenchymal than in parenchymal cells.Key words: LDL, HDL, parenchymal, SR-BI, CD36, selective uptake, cholesterol.


PROTEOMICS ◽  
2011 ◽  
Vol 11 (17) ◽  
pp. 3556-3564 ◽  
Author(s):  
Wei Liu ◽  
Yufang Hou ◽  
Huahai Chen ◽  
Handong Wei ◽  
Weiran Lin ◽  
...  

Author(s):  
Isaac Mohar ◽  
Katherine J. Brempelis ◽  
Sara A. Murray ◽  
Mohammad R. Ebrahimkhani ◽  
I. Nicholas Crispe

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1069 ◽  
Author(s):  
Chang ◽  
Tian ◽  
Ji ◽  
Zhou ◽  
Hou ◽  
...  

Hepatocytes are the main parenchymal cells of the liver and play important roles in liver homeostasis and disease process. The heterogeneity of normal hepatocytes has been reported, but there is little knowledge about hepatocyte subtype and distinctive functions during liver cholestatic injury. Bile duct ligation (BDL)-induced mouse liver injury model was employed, and single-cell RNA sequencing was performed. Western blot and qPCR were used to study gene expression. Immunofluoresence was employed to detect the expressions of marker genes in hepatocytes. We detected a specific hepatocyte cluster (BDL-6) expressing extracellular matrix genes, indicating these hepatocytes might undergo epithelia-mesenchymal transition. Hepatocytes of BDL-6 also performed tissue repair functions (such as angiogenesis) during cholestatic injury. We also found that four clusters of cholestatic hepatocytes (BDL-2, BDL-3, BDL-4, and BDL-5) were involved in inflammatory process in different ways. To be specific, BDL-2/3/5 were inflammation-regulated hepatocytes, while BDL-4 played a role in cell chemotaxis. Among these four clusters, BDL-5 was special. because the hepatocytes of BDL-5 were proliferating hepatocytes. Our analysis provided more knowledge of hepatocyte distinctive functions in injured liver and gave rise to future treatment aiming at hepatocytes.


2021 ◽  
Vol 3 (Supplement_2) ◽  
pp. ii13-ii13
Author(s):  
Roland Kälin ◽  
Linzhi Cai ◽  
Yuping Li ◽  
Louisa von Baumgarten ◽  
Christian Schulz ◽  
...  

Abstract Aggressive brain tumors like glioblastoma depend on support by their local environment and subsets of tumor parenchymal cells may promote specific phases of disease progression. We investigated the glioblastoma microenvironment with transgenic lineage-tracing models, intravital imaging, single-cell transcriptomics, immunofluorescence analysis as well as histopathology and characterized a previously unacknowledged population of tumor-associated cells with a myeloid-like expression profile (TAMEP) that transiently appeared during glioblastoma growth. TAMEP of mice and humans were identified with specific markers. Notably, TAMEP did not derive from microglia or peripheral monocytes but were generated by a fraction of CNS-resident, SOX2-positive progenitors. Abrogation of this progenitor cell population, by conditional Sox2-knockout, drastically reduced glioblastoma vascularization and size. Hence, TAMEP emerge as a tumor parenchymal component with a strong impact on glioblastoma progression.


1988 ◽  
Vol 8 (11) ◽  
pp. 4966-4971
Author(s):  
C F Kuo ◽  
K E Paulson ◽  
J E Darnell

In situ hybridization showed that all fetal hepatocytes contain glutamine synthetase (GS) mRNA but that in adult mouse liver, only a single cell layer surrounding the central veins contains GS mRNA. A shift from the fetal to the adult pattern begins within a few days of birth and is complete within 12 days of birth. Since the total GS mRNA and the transcription rate of the single GS gene are similar at birth and in adults, we conclude that there is a generalized reduction in GS transcription for most hepatocytes and a sharp rise in GS transcription for the immediate pericentral cells. This may be a case of positional regulation of specific gene transcription in apparently a single cell lineage.


1964 ◽  
Vol 21 (2) ◽  
pp. 233-244 ◽  
Author(s):  
Nancy L. Trotter

The fine structure of liver 3½ to 72 hours after partial hepatectomy has been compared with that of liver from sham-operated animals; all animals were 60- to 90-day old male mice of the C3H strain. Numerous small bodies with diameters ranging from 300 to 1,000 A have been observed distributed randomly throughout the cytoplasm of the hepatic parenchymal cells at early intervals after partial hepatectomy. In material fixed in osmium tetroxide and embedded in methacrylate, they appear as uniformly electron-opaque bodies, but in permanganate-fixed liver, they display only a peripheral rim of electron-opaque material surrounding a clear core. Each of these cytoplasmic bodies appears to be located within a vesicle. A few of the opaque bodies are also present in sinusoids and in the spaces of Disse; these bodies are not located within vesicular structures. Fat droplets of various sizes are easily distinguished in regenerating liver; with the increase in number of these fat droplets at later postoperative intervals, there occurs a concomitant decrease in the number of cytoplasmic bodies. It is suggested that the cytoplasmic bodies contain some lipid component. Possible explanations of the origin, nature, and fate of the cytoplasmic bodies are discussed.


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