Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Molecular mechanisms involved in adipose tissue-derived stromal cell hepatic conversion

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Nathalie Saulnier

PROVIDER: E-GEOD-18201 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Molecular mechanisms underlying human adipose tissue-derived stromal cells differentiation into a hepatocyte-like phenotype.

Saulnier Nathalie N Piscaglia Anna Chiara AC Puglisi Maria Ausiliatrice MA Barba Marta M Arena Vincenzo V Pani Giovambattista G Alfieri Sergio S Gasbarrini Antonio A Gasbarrini Antonio A

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 20100603 12

<h4>Background</h4>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.<h4>Aim</h4>In this study, we compared the full genome expression profiles of ATSCs cultured for 4 weeks under pro-hepatogenic conditions to undi ...[more]

PMID: 20605541

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Project description:Bone marrow (BM) has been considered so far the reference source for stromal cells (SC) originally called mesenchymal stem cells. Recently human adult adipose tissue (AT) has been reported as a valuable source for the isolation of cells exerting a mesenchymal-like phenotype. Though both BM- and AT- derived stromal cells (BMSC and ATSC) share similar immuno-phenotype and exhibit multi-lineage potential in vitro, a consensual panel of specific markers is still debated and the precise molecular mechanisms governing their differentiated fate are not fully understood. The aim of this study was to compare the genome wide expression profiles of stromal cells isolated from AT and BM and to emphasize the core of MSC stemness properties. Moreover we focused on the molecular characteristics of ATSC, attempting to reveal their specific features.We identified an overlapping dataset of 190 genes commonly regulated by ATSC and BMSC. Among these, we were able to categorize 6 key biological families that could be regarded as a stemness signature that underlie the self-renewal potential and the ability to generate progenitor cells. In particular, a pivotal role of signalling pathways along with the expression of numerous transcription regulators emerged from this study. Genes specifically modulated in ATSC, suggested that these cells posses anti-oxidative and neuroprotective properties. Taken together, these results provide new hints towards the understanding of the molecular basis of MSC maintenance and suggest that ATSC have interesting properties which could be useful for several potential clinical applications. Experiment Overall Design: Bone marrow and adipose tissue samples were respectively obtained from four long-term disease-free Hodgkin lymphoma patients, during follow-up investigation and from four patients subjected to partial abdominoplasty. In addition, we used in this study a cell line (MRC-5 cells) as control to rule out genes involved in homeostasis and emphasize genes specifically expressed in both types of mesenchymal stem cells. To have results statistically significant, we enrolled four patients for each tissue (4 chips/tissue) and we performed a technical replicate (triplicate) for the MRC-5 cells.

Project description:Limbal stromal cells were reported to resemble mesenchymal stem cells (MSCs) with multipotential differentiation cability. However, little is known about their gene expression profiles compared to MSC derived from various sources. In this study, the gene expression profile of limbal stromal cells was compared to bone marrow, adipose stromal cells and foreskin fibroblasts. In addition, we also explored the gene expression changes of ex vivo expanded limbal stromal cells when cultured in two different systems. Expanded limbal stromal cells were divided into two groups; each cultured separately on a matrigel-coated plate in DMEM/F12 medium supplemented with bFGF and LIF and the other on a normal plate in DMEM medium supplemented with 10% fetal bovine serum (FBS). Cryopreserved bone marrow mesenchymal cells, adipose stromal cells and foreskin fibroblasts were cultured-expanded until confluent. Total RNA was extracted from all the samples and subjected to microarray experiments with an Agilent platform by using Human GE 8x60k microarrays. Data analysis was carried out with GeneSpring software. A total of 871 genes were upregulated when the limbal stromal cells were cultured in the matrigel system, whereas 58 genes were consistently differentially expressed in limbal stromal cells compared to other lineages. Besides the long intergenic non-coding RNA and unknown genes, these genes represent gene ontology for cellular components, molecular function and biological process. Samples derived from the same source were closely clustered by Hierachical clustering analysis. The limbal stromal cells have a distinct molecular signature compared to MSCs from other lineages. The culture system affected the gene expression profile of limbal stromal cells tremendously. Derived limbal stromal cells were cultured using two different methods, one with matrigel and the other with FBS. Their gene expression profiles were compared. The gene expression profile of limbal stromal cells that were cultured with FBS also was compared to the gene expression profiles of bone marrow mesenchymal stem cells, adipose stromal cells and foreskin fibroblasts.

Project description:The raw files of the proteomics dataset are N=18 and a brief description of the files is shown below: AF1 raw: exosomes derived from Amniotic Fluid-Mesenchymal Stromal cells 1 AF2.raw: exosomes derived from Amniotic Fluid-Mesenchymal Stromal cells 2 AFA1.raw: exosomes derived from Amniotic Fluid-Mesenchymal Stromal cells 3 AFA2.raw: exosomes derived from Amniotic Fluid-Mesenchymal Stromal cells 4 AFB1.raw: exosomes derived from Amniotic Fluid-Mesenchymal Stromal cells 5 AFB2.raw: exosomes derived from Amniotic Fluid-Mesenchymal Stromal cells 6 HL1A.raw: exosomes derived from Hepatocyte like cells 1 HL1B.raw: exosomes derived from Hepatocyte like cells 2 HL2A.raw: exosomes derived from Hepatocyte like cells 3 HL2B.raw: exosomes derived from Hepatocyte like cells 4 HL3A.raw: exosomes derived from Hepatocyte like cells 5 HL3B.raw: exosomes derived from Hepatocyte like cells 6 HPLA1.raw: exosomes derived from Hepatic Progenitor-like cells 1 HPLA2.raw: exosomes derived from Hepatic Progenitor-like cells 2 HPLB1.raw: exosomes derived from Hepatic Progenitor-like cells 3 HPLB2.raw: exosomes derived from Hepatic Progenitor-like cells 4 HPLA.raw: exosomes derived from Hepatic Progenitor-like cells 5 HPLB.raw: exosomes derived from Hepatic Progenitor-like cells 6 Raw files analysis was performed with Proteome Discoverer 1.4 (Thermo) software package, using the Sequest search engine and the Uniprot human (Homo sapiens) reviewed database, downloaded on December 15, 2017, including 20,243 entries. The search was performed using carbamidomethylation of cysteine as static and oxidation of methionine as dynamic modifications. Two missed cleavage sites, a precursor mass tolerance of 10 ppm and fragment mass tolerance of 0.05 Da were allowed. False discovery rate (FDR) validation was based on q value: target FDR : 0.05. Label free quantification was performed by utilizing the precursor ion area values exported from the total ion chromatogram as defined by the Proteome Discoverer v. 1.4.0.288 (Thermo Scientific). Output files from Proteome Discoverer were processed with R programming language for statistical computing (version 4.0.3). The following comparisons were made: AF vs HL, AF vs HPL and HL vs HPL. The msf files are N=18 and have the same name as the raw files above.

Dataset Information

Molecular mechanisms involved in adipose tissue-derived stromal cell hepatic conversion

Publications

Molecular mechanisms underlying human adipose tissue-derived stromal cells differentiation into a hepatocyte-like phenotype.

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