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题目:: Molecular mechanisms involved in adipose tissue-derived stromal cell hepatic conversion
ID:
状态:: 发布时间Dec. 14, 2009 , 更新时间 May 1, 2014
物种:: Homo sapiens
摘要:: Background: Adipose tissue-derived stromal cells (ATSCs) hold great promises in regenerative medicine, due to their easy retrieval, high proliferative capacity, and multi-lineage differentiation potential. In the last decade, several studies have reported the plasticity of ATSCs toward a hepatic fate. Nonetheless, the molecular mechanisms underlying the conversion from a mesenchymal to an epithelial phenotype remain poorly understood. Aim: In this study, we compared the full genome expression profiles of ATSCs cultured for 4 weeks under pro-hepatogenic conditions to undifferentiated ATSCs, in order to depict the molecular events involved in ATSC hepatic transdifferentiation. Methods: Molecular analysis was performed using the Affymetrix human focus arrays. Sets of differentially expressed genes were functionally categorized in order to understand which pathways drive the hepatic conversion and interesting target genes were validated by Q-PCR. Results: We showed that ATSC-derived hepatocyte-like cells activate several genes associated with specific liver functions, including protein metabolism, innate immune response regulation, and biodegradation of toxic compounds. Furthermore, microarray analysis highlighted the downregulation of several transcripts involved in stemness maintenance along with genes associated with a mesenchymal phenotype. Conclusion: Taken together, our data suggest that the in vitro system used in this study drove ATSCs toward a hepatic conversion through a subtle regulation of molecular pathways controlling stem cell properties and lineage commitment that promote mesenchymal-epithelial-transition. Adipose tissue was obtained from 3 patients undergoing partial abdominoplasty. Adipose tissue-derived stromal cells (ATSC) were isolated according to standard procedures, using the in vitro adherence property of these cells. At passage culture 4, ATSC were submitted to an in vitro hepatogenic regimen, consisting of the sequential addition of growth factors. After 1 month of in vitro differentiation, cells were harvested and their transcriptome was compared to control ATSC.
实验种类:: transcription profiling by array
样本量:: 6
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数据号:: E-GEOD-18201, GSE18201
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