Epigenetic Memory of HSC after LPS injection (ATAC-Seq)

Here we show that immune challenge can induce epigenetic memory in HSC. We show that LPS, a gram-negative bacterial component, induces changes in HSC differentiation and gene expression that returned rapidly to normal but also establish novel open chromatin regions (OCR) that persist long term. These OCR are associated with genes involved in myeloid lineage commitment and innate immunity, that become more highly expressed upon a secondary bacterial challenge and enable LPS-exposed HSCs to mount an increased myeloid differentiation and accelerated immune response. Overall design: Mice were injected with 125 ug of LPS IP or PBS. ATAC-seq was performed on HSC KSL Flt3- sorted 0, 4 weeks or 12 weeks after LPS injection. Samples are from pool of 4-8 mice.

我们的研究证实，免疫刺激可在造血干细胞（Hematopoietic Stem Cell, HSC）中诱导表观遗传记忆。研究发现，革兰氏阴性菌组分脂多糖（Lipopolysaccharide, LPS）可引发造血干细胞的分化与基因表达改变，此类改变可快速恢复至正常水平，但同时也会建立新的开放染色质区域（open chromatin regions, OCR）并长期维持。这些开放染色质区域与髓系谱系定向及固有免疫相关基因相关联；当遭遇二次细菌刺激时，这些基因的表达水平会进一步升高，使得预先暴露于脂多糖的造血干细胞能够启动更强的髓系分化应答与加速的免疫反应。
实验整体设计：小鼠经腹腔注射125 μg脂多糖或磷酸盐缓冲液（Phosphate Buffered Saline, PBS）；分别于注射后0、4周或12周，对分选得到的KSL+Flt3-造血干细胞进行转座酶可及性测序（ATAC-seq）；所有样本均取自4-8只小鼠的混合样本。