Adipose-derived stem cells (ADSCs) are stromal mesenchymal stem cells isolated from lipoaspirates, and they display a broad potential to differentiate toward different lineages. The role of epigenetics in regulating the expression of their lineage-specific genes is under evaluation, however till date virtually nothing is known about the relative significance of cardiac-specific transcription factor genes in human ADSCs. The aim of this study was to investigate DNA promoter methylation and relevant histone modifications involving MEF-2C, GATA-4, and Nkx2.5 in native human ADSCs. CpG sites at the transcription start in their promoters were found unmethylated using methylation-specific PCR. Chromatin immunoprecipitation assay showed low levels of total acetylated H3 histone (acH3) and high levels of trimethylated lysine 27 in H3 histone (H3K27me3) which were associated with both GATA-4 and Nkx2.5 promoters, indicating their transcriptional repressive chromatin arrangement. On the other hand, the opposite was apparent for MEF-2C promoter. Accordingly, MEF-2C—but not GATA-4 and Nkx2.5— transcripts were evidenced in native human ADSCs. These results suggest that the chromatin arrangement of these early cardiac regulatory genes could be explored as a level of intervention to address the differentiation of human ADSCs toward the cardiac lineage.

Epigenetic signature of early cardiac regulatory genes in human adipose-derived stem cells

PASINI, ALICE;BONAFÈ, FRANCESCA;GOVONI, MARCO;GUARNIERI, CARLO;MORSELLI, PAOLO;MUSCARI, CLAUDIO;GIORDANO, EMANUELE DOMENICO
2013

Abstract

Adipose-derived stem cells (ADSCs) are stromal mesenchymal stem cells isolated from lipoaspirates, and they display a broad potential to differentiate toward different lineages. The role of epigenetics in regulating the expression of their lineage-specific genes is under evaluation, however till date virtually nothing is known about the relative significance of cardiac-specific transcription factor genes in human ADSCs. The aim of this study was to investigate DNA promoter methylation and relevant histone modifications involving MEF-2C, GATA-4, and Nkx2.5 in native human ADSCs. CpG sites at the transcription start in their promoters were found unmethylated using methylation-specific PCR. Chromatin immunoprecipitation assay showed low levels of total acetylated H3 histone (acH3) and high levels of trimethylated lysine 27 in H3 histone (H3K27me3) which were associated with both GATA-4 and Nkx2.5 promoters, indicating their transcriptional repressive chromatin arrangement. On the other hand, the opposite was apparent for MEF-2C promoter. Accordingly, MEF-2C—but not GATA-4 and Nkx2.5— transcripts were evidenced in native human ADSCs. These results suggest that the chromatin arrangement of these early cardiac regulatory genes could be explored as a level of intervention to address the differentiation of human ADSCs toward the cardiac lineage.
Pasini A; Bonafè F; Govoni M; Guarnieri C; Morselli PG; Sharma HS; Caldarera CM; Muscari C; GIORDANO E
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/154336
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