Department of Haematology, University of Cambridge, Cambridge, CB2 0XY, UK.
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, CB10 1SA, UK.
Nat Commun. 2017 Dec 11;8(1):2045. doi: 10.1038/s41467-017-02305-6.
The success of marker-based approaches for dissecting haematopoiesis in mouse and human is reliant on the presence of well-defined cell surface markers specific for diverse progenitor populations. An inherent problem with this approach is that the presence of specific cell surface markers does not directly reflect the transcriptional state of a cell. Here, we used a marker-free approach to computationally reconstruct the blood lineage tree in zebrafish and order cells along their differentiation trajectory, based on their global transcriptional differences. Within the population of transcriptionally similar stem and progenitor cells, our analysis reveals considerable cell-to-cell differences in their probability to transition to another committed state. Once fate decision is executed, the suppression of transcription of ribosomal genes and upregulation of lineage-specific factors coordinately controls lineage differentiation. Evolutionary analysis further demonstrates that this haematopoietic programme is highly conserved between zebrafish and higher vertebrates.
基于标志物的方法在解析小鼠和人类造血方面取得了成功,这依赖于存在针对不同祖细胞群体的明确的细胞表面标志物。这种方法的一个固有问题是,特定细胞表面标志物的存在并不直接反映细胞的转录状态。在这里,我们使用无标记的方法,基于它们的全局转录差异,在斑马鱼中计算性地重建血液谱系树,并沿着它们的分化轨迹对细胞进行排序。在转录相似的干细胞和祖细胞群体中,我们的分析揭示了它们向另一个定向状态转变的概率存在相当大的细胞间差异。一旦命运决定被执行,核糖体基因转录的抑制和谱系特异性因子的上调协调控制谱系分化。进化分析进一步表明,这种造血程序在斑马鱼和高等脊椎动物之间高度保守。