DNA Methylation and Hydroxymethylation Profile of CD34+-Enriched Cell Products Intended for Autologous CD34+ Cell Transplantation.
Epigenetic dysregulation has been shown to limit functional capacity of aging hematopoietic stem cells, which may contribute to impaired outcome of hematopoietic stem cell-based therapies. The aim of our study was to gain better insight into the epigenetic profile of CD34+-enriched cell products intended for autologous CD34+ cell transplantation in patients with cardiomyopathy. We found global DNA methylation content significantly higher in immunoselected CD34+ cells compared to leukocytes in leukapheresis products (2.33 ± 1.03% vs. 1.84 ± 0.86%, p = 0.04). Global DNA hydroxymethylation content did not differ between CD34+ cells and leukocytes (p = 0.30). By measuring methylation levels of 94 stem cell transcription factors on a ready-to-use array, we identified 15 factors in which average promoter methylation was significantly different between leukocytes and CD34+ cells. The difference was highest for HOXC12 (58.18 ± 6.47% vs. 13.34 ± 24.18%, p = 0.0009) and NR2F2 (51.65 ± 25.89% vs. 7.66 ± 21.43%, p = 0.0045) genes. Our findings suggest that global DNA methylation and hydroxymethylation patterns as well as target methylation profile of selected genes in CD34+-enriched cell products do not differ significantly compared to leukapheresis products and, thus, can tell us little about the functional capacity and regenerative properties of CD34+ cells. Future studies should examine other CD34+ cell graft characteristics, which may serve as prognostic tools for autologous CD34+ cell transplantation.
['Rozman|Jasmina-Ziva|JZ|', 'Pohar Perme|Maja|M|', 'Jez|Mojca|M|', 'Malicev|Elvira|E|', 'Krasna|Metka|M|', 'Vrtovec|Bojan|B|', 'Rozman|Primoz|P|']
D000328:Adult D018952:Antigens, CD34 D064592:Autografts D051837:COUP Transcription Factor II D009202:Cardiomyopathies D004247:DNA D019175:DNA Methylation D044127:Epigenesis, Genetic D005260:Female D018380:Hematopoietic Stem Cell Transplantation D006801:Humans D008297:Male D008875:Middle Aged D014157:Transcription Factors
DNA methylation CD34+ cell epigenetics cell-based therapy DNA hydroxymethylation heart failure