Hematopoietic stem/progenitor cell senescence is associated with altered expression profiles of cellular memory-involved gene.

To evaluate the contributions of cellular memory mechanisms to hematopoietic stem/progenitor cell (HSPC) senescence. HSPCs (LinCD117, hereafter referred to as HSPC) were separated from young (6-week-old) and aged (18-month-old) mice using Magnetic Activated Cell Sorting (MACS). Cell cycle distribution of HSPCs was determined using flow cytometry. The mixed colony forming unit (CFU-Mix) assay was used to study the HSPCs' ability to proliferate. The mRNA expression levels of cellular memory-implicated PCG family (enhancer of zeste homolog 2 (Ezh2), B lymphoma mo-MLV insertion region 1 (Bmi-1), embryonic ectoderm development (Eed), melanoma nuclear protein 18 (Mel18), Mph1/polyhomeotic-like protein 1 (Rae-28)) and Trithorax group (TrxG) family (mixed lineage leukemia (Mll), thioredoxin (Trx)) were determined by quantitative real-time PCR. We obtained highly purified populations of mouse HSPCs (LinCD117) (92.2 ± 4.5% CD117). The percentage of HSPCs was significantly higher in older mice compared with younger control mice and the percentage of SA-β-galactosidase positive cells was significantly higher in HSPCs isolated from older mice (<0.05). The percentage of HSPCs in G/G was significantly higher in older mice compared with younger control mice (52.0 compared with 47.1%), indicating increased cell cycle arrest in senescent HSPCs. The amount of CFU-Mix was significantly decreased in aged group (13.8 compared with 40.0), indicating a diminished ability to proliferate in senescent HSPCs. gene mRNA expression was significantly lower in HSPCs from older mice compared to younger controls, while mRNA expression was significantly higher in HSPCs from older mice (<0.05). The expression of genes associated with cellular memory is altered in senescent (Lin CD117) HSPCs, which may affect the potential plasticity of aged hematopoietic stem cells (HSCs) and thereby contribute to senescence-associated disease processes.