Epigenetic traits inscribed in chromatin accessibility in aged hematopoietic stem cells(ATAC-seq in cytokine and LPS:polyIpolyC experiments))

Aging of the hematopoietic system is associated with cytopenia and increased risk of hematological malignancies. To investigate cell-intrinsic factors underlying aging of hematopoiesis, we profiled transcriptome, chromatin accessibility, histone modifications in young and aged Hematopoietic stem cells (HSCs) and progenitors. Various differentially expressed genes were detected in each fraction. Changes of transcriptome were more drastic in progenitors than in HSCs. In contrast, aberrant chromatin accessible regions were accumulated particularly in aged HSCs without affecting steady-state transcriptions of nearest genes. These regions were enriched for motif of STAT3, STAT5, c-Jun-CRE, NF-E2, NRF2. We also found H3K27me3 marked genes and bivalent genes were substantially decreased in aged HSCs, some of which became active state and some of which became more repressive state with increased DNA methylation. Our data indicates that integrated analysis of epigenome and transcriptome provides more profound insights into aging of hematopoietic systems. ATAC-seq before and after cytokine stimulation(3h) and PBS treatments and LPS:polyIpolyC treatments.