Molecular mechanisms underlying human adipose tissue-derived stromal cells differentiation into a hepatocyte-like phenotype.
BACKGROUND
Adipose tissue-derived stromal cells (ATSCs) hold great promises in regenerative medicine. In the last decade, several studies have reported the plasticity of ATSCs toward a hepatocyte-like phenotype. Nonetheless, the molecular mechanisms underlying the conversion from a mesenchymal to an epithelial phenotype remain poorly understood.


OBJECTIVE
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
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 targets were validated by Q-PCR.


RESULTS
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 downregulation of transcripts associated with the mesenchymal lineage, while epithelial-related genes were overexpressed.


CONCLUSIONS
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 lineage commitment that promote mesenchymal-epithelial transition.
Saulnier
Nathalie
N
GI & Liver Stem Cell Research Group (GILSteR), Department of Internal Medicine and Gastroenterology, Gemelli Hospital, Catholic University of Rome, Rome, Italy. nathalie.saulnier@rm.unicatt.it
Piscaglia
Anna Chiara
AC
Puglisi
Maria Ausiliatrice
MA
Barba
Marta
M
Arena
Vincenzo
V
Pani
Giovambattista
G
Alfieri
Sergio
S
Gasbarrini
Antonio
A
D000273:Adipose Tissue / Q000166:cytology*; D002454:Cell Differentiation / Q000235:genetics; D022781:Hepatocytes / Q000166:cytology* / Q000502:physiology; D006801:Humans; D010641:Phenotype; D017154:Stromal Cells / Q000166:cytology* / Q000502:physiology