Lineage-specific promoter DNA methylation patterns segregate adult progenitor cell types.
Mesenchymal stem cells (MSCs) can differentiate into multiple mesodermal cell types in vitro; however, their differentiation capacity is influenced by their tissue of origin. To what extent epigenetic information on promoters of lineage-specification genes in human progenitors influences transcriptional activation and differentiation potential remains unclear. We produced bisulfite sequencing maps of DNA methylation in adipogenic, myogenic, and endothelial promoters in relation to gene expression and differentiation capacity, and unravel a similarity in DNA methylation profiles between MSCs isolated from human adipose tissue, bone marrow (BM), and muscle. This similarity is irrespective of promoter CpG content. Methylation patterns of MSCs are distinct from those of hematopoietic progenitor cells (HPCs), pluripotent human embryonic stem cells (hESCs), and multipotent hESC-derived mesenchymal cells (MCs). Moreover, in vitro MSC differentiation does not affect lineage-specific promoter methylation states, arguing that these methylation patterns in differentiated cells are already established at the progenitor stage. Further, we find a correlation between lineage-specific promoter hypermethylation and lack of differentiation capacity toward that lineage, but no relationship between weak promoter methylation and capacity of transcriptional activation or differentiation. Thus, only part of the restriction in differentiation capacity of tissue-specific stem cells is programmed by promoter DNA methylation: hypermethylation seems to constitute a barrier to differentiation, however, no or weak methylation has no predictive value for differentiation potential.
Sørensen
Anita L
AL
Department of Biochemistry, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo and Norwegian Center for Stem Cell Research, Oslo, Norway.
Timoskainen
Sanna
S
West
Franklin D
FD
Vekterud
Kristin
K
Boquest
Andrew C
AC
Ahrlund-Richter
Lars
L
Stice
Steve L
SL
Collas
Philippe
P
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology; D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D032342:Muscle Cells / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*
D019408:Platelet Endothelial Cell Adhesion Molecule-1