Dynamics of chromatin and transcriptome in the HSPCs at different hematopoietic developmental stages [RNA-seq]

ATAC-seq and RNA-seq were used to compare the chromatin states and corresponding transcriptomes of developing HSPC. We found that the chromatin states and transcriptomes change markedly when HSPCs migrate from PL to FL and from FL to BM. Then we compared chromatin among E12.5 PL, E12.5 FL, and E16.5 FL, the proportion of fragments in the nucleosome-free region significantly increases in E12.5 and E16.5 FL-HSPCs compared with E12.5 PL-HSPCs; the motifs of ETS and Runt are enriched at the opening or closing peaks from E12.5 PL to E12.5 FL and E12.5 FL to E16.5 FL, and the expression of these factors is either up-regulated or down-regulated; the motifs of bZIP and Zf are enriched at the closing and opening peaks from E12.5 PL to E12.5 FL and E12.5 FL to E16.5 FL respectively, In line, the expression of these factors is down-regulated or up-regulated. RNA-seq本研究采用转座酶可及性测序（ATAC-seq）与RNA测序（RNA-seq），对发育过程中造血干细胞与祖细胞（hematopoietic stem and progenitor cells, HSPC）的染色质状态及其对应转录组开展比较分析。结果显示，当HSPC从胎盘（placenta, PL）迁移至胎肝（fetal liver, FL）、再从胎肝迁移至骨髓（bone marrow, BM）时，其染色质状态与转录组均发生显著改变。随后，我们对胚胎第12.5天胎盘来源HSPC（E12.5 PL-HSPC）、胚胎第12.5天胎肝来源HSPC（E12.5 FL-HSPC）以及胚胎第16.5天胎肝来源HSPC（E16.5 FL-HSPC）的染色质开放特征进行比较，发现相较于E12.5 PL-HSPC，E12.5 FL-HSPC与E16.5 FL-HSPC的无核小体区域片段占比显著升高；ETS与Runt家族的结合基序在E12.5 PL向E12.5 FL、以及E12.5 FL向E16.5 FL迁移过程中的染色质开放/关闭峰中显著富集，且对应调控因子的表达呈现上调或下调变化；而碱性亮氨酸拉链（basic leucine zipper, bZIP）与锌指（zinc finger, Zf）家族的结合基序则分别在E12.5 PL向E12.5 FL迁移过程中的关闭峰、以及E12.5 FL向E16.5 FL迁移过程中的开放峰中富集，与此一致，这两类调控因子的表达分别呈现下调与上调趋势。RNA-seq