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Oxygen drives hepatocyte differentiation and phenotype stability in liver cell lines

Overview of attention for article published in Journal of Cell Communication and Signaling, February 2018
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3 tweeters

Citations

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4 Dimensions

Readers on

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15 Mendeley
Title
Oxygen drives hepatocyte differentiation and phenotype stability in liver cell lines
Published in
Journal of Cell Communication and Signaling, February 2018
DOI 10.1007/s12079-018-0456-4
Pubmed ID
Authors

Martien van Wenum, Aziza A. A. Adam, Vincent A. van der Mark, Jung-Chin Chang, Manon E. Wildenberg, Erik J. Hendriks, Aldo Jongejan, Perry D. Moerland, Thomas M. van Gulik, Ronald P. Oude Elferink, Robert A. F. M. Chamuleau, Ruurdtje Hoekstra

Abstract

The in vitro generation of terminally differentiated hepatocytes is an unmet need. We investigated the contribution of oxygen concentration to differentiation in human liver cell lines HepaRG and C3A. HepaRG cells were cultured under hypoxia (5%O2), normoxia (21%O2) or hyperoxia (40%O2). Cultures were analysed for hepatic functions, gene transcript levels, and protein expression of albumin, hepatic transcription factor CEBPα, hepatic progenitor marker SOX9, and hypoxia inducible factor (HIF)1α. C3A cells were analysed after exposure to normoxia or hyperoxia. In hyperoxic HepaRG cultures, urea cycle activity, bile acid synthesis, CytochromeP450 3A4 (CYP3A4) activity and ammonia elimination were 165-266% increased. These effects were reproduced in C3A cells. Whole transcriptome analysis of HepaRG cells revealed that 240 (of 23.223) probes were differentially expressed under hyperoxia, with an overrepresentation of genes involved in hepatic differentiation, metabolism and extracellular signalling. Under hypoxia, CYP3A4 activity and ammonia elimination were inhibited almost completely and 5/5 tested hepatic genes and 2/3 tested hepatic transcription factor genes were downregulated. Protein expression of SOX9 and HIF1α was strongly positive in hypoxic cultures, variable in normoxic cultures and predominantly negative in hyperoxic cultures. Conversely, albumin and CEBPα expression were highest in hyperoxic cultures. HepaRG cells that were serially passaged under hypoxia maintained their capacity to differentiate under normoxia, in contrast to cells passaged under normoxia. Hyperoxia increases hepatocyte differentiation in HepaRG and C3A cells. In contrast, hypoxia maintains stem cell characteristics and inhibits hepatic differentiation of HepaRG cells, possibly through the activity of HIF1α.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 15 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 15 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 6 40%
Unspecified 3 20%
Researcher 3 20%
Student > Ph. D. Student 2 13%
Student > Bachelor 1 7%
Other 0 0%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 27%
Unspecified 4 27%
Agricultural and Biological Sciences 3 20%
Medicine and Dentistry 2 13%
Pharmacology, Toxicology and Pharmaceutical Science 1 7%
Other 1 7%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 February 2018.
All research outputs
#7,544,213
of 12,510,237 outputs
Outputs from Journal of Cell Communication and Signaling
#57
of 136 outputs
Outputs of similar age
#179,337
of 341,330 outputs
Outputs of similar age from Journal of Cell Communication and Signaling
#2
of 10 outputs
Altmetric has tracked 12,510,237 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 136 research outputs from this source. They receive a mean Attention Score of 2.3. This one has gotten more attention than average, scoring higher than 55% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 341,330 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 10 others from the same source and published within six weeks on either side of this one. This one has scored higher than 8 of them.