Cells with slow proliferation kinetics that retain the nuclear label over long time periods – the label-retaining cells (LRCs) – represent multipotent stem cells in a number of adult tissues. Since the identity of liver LRCs (LLRCs) had remained elusive we utilized a genetic approach to reveal LLRCs in normal non-injured livers and characterized their regenerative properties in vivo and in culture. We found that LLRCs were located in biliary vessels and participated in the regeneration of biliary but not hepatocyte injury. In culture experiments the sorted LLRCs displayed an enhanced self-renewal capacity but a unipotent biliary differentiation potential. Transcriptome analysis revealed a unique set of tumorigenesis- and nervous system-related genes upregulated in LLRCs when compared to non-LRC cholangiocytes. We conclude that the LLRCs established during the normal morphogenesis of the liver do not represent a multipotent primitive somatic stem cell population but act as unipotent biliary progenitor cells. Overall design: Transcriptome comparison of label-retaining biliary epithelial cells and non-label-retaining biliary epithelial cells (cells with GFP expression were compared to the cells without GFP). Illumina HiSeq 2000 was used to analyze 8 RNA samples from 4 mice.
A label-retaining but unipotent cell population resides in biliary compartment of mammalian liver.
Subject
View SamplesTherapeutic hypothermia is a clinically effective treatment for various hypoxic and ischemic conditions, but the associated molecular mechanisms remain unclear. To gain insight into hypothermia-induced transcriptional response, mouse embryonic fibroblasts were exposed to mild hypothermia (32C) or normothermia (37C) for increasing time periods. We aimed to identify genes with temporally near-monotonic response as the most obvious candidates for mediating the therapeutic effects of hypothermia.
Estimating differential expression from multiple indicators.
Specimen part, Time
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