Gene profiling of bone marrow- and adipose tissue-derived stromal cells: a key role of Kruppel-like factor 4 in cell fate regulation.
OBJECTIVE
Bone marrow- and adipose tissue-derived mesenchymal stromal cells (MSC) represent promising sources for regenerative medicine. However, the precise molecular mechanisms underlying MSC stemness maintenance versus differentiation are not fully understood. The aim of this study was to compare the genome-wide expression profiles of bone marrow-and adipose tissue-derived MSC, in order to identify a common molecular stemness core.


METHODS
Molecular profiling was carried out using Affymetrix microarray and relevant genes were further validated by Q-PCR.


RESULTS
We identified an overlapping dataset of 190 transcripts commonly regulated in both cell populations, which included several genes involved in stemness regulation (i.e. self-renewal potential and the ability to generate differentiated cells), various signaling pathways and transcription factors. In particular, we identified a central role of the Kruppel-like factor 4 (KLF4) DNA-binding protein in regulating MSC transcriptional activity.


CONCLUSIONS
Our results provide new insights toward understanding the molecular basis of MSC stemness maintenance and underline the ability of KLF4 to maintain cells in an undifferentiated state.
Saulnier
Nathalie
N
Department of Internal Medicine and Gastroenterology, Gemelli University Hospital, Catholic University of Sacred Heart, Rome, Italy. nathaliesaulnier@yahoo.fr
Puglisi
Maria A
MA
Lattanzi
Wanda
W
Castellini
Laura
L
Pani
Giovambattista
G
Leone
Giuseppe
G
Alfieri
Sergio
S
Michetti
Fabrizio
F
Piscaglia
Anna Chiara
AC
Gasbarrini
Antonio
A
D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D001665:Binding Sites; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D008954:Models, Biological; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D015203:Reproducibility of Results; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D055815:Young Adult
C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors