Epigenetic signatures associated with different levels of differentiation potential in human stem cells.
BACKGROUND
The therapeutic use of multipotent stem cells depends on their differentiation potential, which has been shown to be variable for different populations. These differences are likely to be the result of key changes in their epigenetic profiles.


RESULTS
to address this issue, we have investigated the levels of epigenetic regulation in well characterized populations of pluripotent embryonic stem cells (ESC) and multipotent adult stem cells (ASC) at the trancriptome, methylome, histone modification and microRNA levels. Differences in gene expression profiles allowed classification of stem cells into three separate populations including ESC, multipotent adult progenitor cells (MAPC) and mesenchymal stromal cells (MSC). The analysis of the PcG repressive marks, histone modifications and gene promoter methylation of differentiation and pluripotency genes demonstrated that stem cell populations with a wider differentiation potential (ESC and MAPC) showed stronger representation of epigenetic repressive marks in differentiation genes and that this epigenetic signature was progressively lost with restriction of stem cell potential. Our analysis of microRNA established specific microRNA signatures suggesting specific microRNAs involved in regulation of pluripotent and differentiation genes.


CONCLUSIONS
Our study leads us to propose a model where the level of epigenetic regulation, as a combination of DNA methylation and histone modification marks, at differentiation genes defines degrees of differentiation potential from progenitor and multipotent stem cells to pluripotent stem cells.
Aranda
Pablo
P
Hematology Department and Area of Cell Therapy, Clínica Universidad de Navarra, Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain.
Agirre
Xabier
X
Ballestar
Esteban
E
Andreu
Enrique J
EJ
Román-Gómez
José
J
Prieto
Inés
I
Martín-Subero
José Ignacio
JI
Cigudosa
Juan Cruz
JC
Siebert
Reiner
R
Esteller
Manel
M
Prosper
Felipe
F
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D002454:Cell Differentiation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D006657:Histones / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D013234:Stem Cells / Q000166:cytology*; D014158:Transcription, Genetic
D006657:Histones; D035683:MicroRNAs