Dorn Isabel, Klich Katharina, Arauzo-Bravo Marcos J, Radstaak Martina, Santourlidis Simeon, Ghanjati Foued, Radke Teja F, Psathaki Olympia E, Hargus Gunnar, Kramer Jan, Einhaus Martin, Kim Jeong Beom, Kögler Gesine, Wernet Peter, Schöler Hans R, Schlenke Peter, Zaehres Holm
Max Planck Institute for Molecular Biomedicine, Münster, Germany Pediatric Hematology and Oncology, University Hospital Münster, Germany
Max Planck Institute for Molecular Biomedicine, Münster, Germany Institute for Transfusion Medicine and Transplantation Immunology, University Hospital Münster, Germany.
Haematologica. 2015 Jan;100(1):32-41. doi: 10.3324/haematol.2014.108068. Epub 2014 Oct 17.
Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34(+) hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex vivo expansion of induced pluripotent stem cells into erythroid cells, we compared induced pluripotent stem cells from human neural stem cells and human cord blood-derived CD34(+) hematopoietic stem cells and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells. Although genome-wide DNA methylation profiling at all promoter regions demonstrates that the epigenetic memory of induced pluripotent stem cells is influenced by the somatic cell type of origin of the stem cells, we found a similar hematopoietic induction potential and erythroid differentiation pattern of induced pluripotent stem cells of different somatic cell origin. All human induced pluripotent stem cell lines showed terminal maturation into normoblasts and enucleated reticulocytes, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the induced pluripotent stem cells derived from CD34(+) hematopoietic stem cells. More detailed methylation analysis of the hematopoietic and erythroid promoters identified similar CpG methylation levels in the induced pluripotent stem cell lines derived from CD34(+) cells and those derived from neural stem cells, which confirms their comparable erythroid differentiation potential.
诱导多能干细胞中的表观遗传记忆与干细胞的体细胞起源类型相关，可能导致多能干细胞分化能力的差异。在这种情况下，源自人CD34(+)造血干细胞的诱导多能干细胞可能比常用的成纤维细胞来源的诱导多能干细胞更适合造血分化。为了研究表观遗传记忆对诱导多能干细胞体外扩增为红系细胞的影响，我们比较了源自人神经干细胞和人脐带血来源的CD34(+)造血干细胞的诱导多能干细胞，并评估了它们分化为造血祖细胞和成熟红细胞的潜力。尽管所有启动子区域的全基因组DNA甲基化分析表明，诱导多能干细胞的表观遗传记忆受干细胞体细胞起源类型的影响，但我们发现不同体细胞起源的诱导多能干细胞具有相似的造血诱导潜力和红系分化模式。所有人类诱导多能干细胞系均显示终末成熟为成红细胞和去核网织红细胞，主要产生胎儿血红蛋白。仅在红系细胞的生长速率上观察到差异，源自CD34(+)造血干细胞的诱导多能干细胞中的生长速率略高。对造血和红系启动子进行更详细的甲基化分析发现，源自CD34(+)细胞的诱导多能干细胞系和源自神经干细胞的诱导多能干细胞系中具有相似的CpG甲基化水平，这证实了它们相当的红系分化潜力。
