Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.
Science. 2014 Sep 26;345(6204):1251033. doi: 10.1126/science.1251033.
Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (NFIB) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.
血细胞由造血干细胞通过逐步的命运事件产生。为了描述驱动谱系选择的基因表达程序，我们对来自 8 个人类主要造血祖细胞群体的 RNA 进行了测序，这些细胞代表了主要的髓系定向阶段和主要的淋巴样阶段。我们发现了广泛的细胞类型特异性表达变化：6711 个基因和 10724 个转录本，在分化的早期阶段富含非蛋白编码元件。此外，我们还发现了 7881 个新的剪接接头和 2301 个差异使用的选择性剪接事件，这些事件富含参与调控过程的基因。我们通过实验证明了细胞特异性异构体的使用，确定核因子 I/B（NFIB）是巨核细胞成熟（血小板前体）的调节因子。我们的数据突出了密切相关的祖细胞群体中命运事件的复杂性，理解这一点对于推进移植和再生医学至关重要。
