Hamey Fiona K, Göttgens Berthold
Department of Haematology, Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Methods Mol Biol. 2019;1975:239-249. doi: 10.1007/978-1-4939-9224-9_11.
Hematopoietic stem cells (HSCs) reside at the apex of the hematopoietic hierarchy, possessing the ability to self-renew and differentiate toward all mature blood lineages. Along with more specialized progenitor cells, HSCs have an essential role in maintaining a healthy blood system. Incorrect regulation of cell fate decisions in stem/progenitor cells can lead to an imbalance of mature blood cell populations-a situation seen in diseases such as leukemia. Transcription factors, acting as part of complex regulatory networks, are known to play an important role in regulating hematopoietic cell fate decisions. Yet, discovering the interactions present in these networks remains a big challenge. Here, we discuss a computational method that uses single-cell gene expression data to reconstruct Boolean gene regulatory network models and show how this technique can be applied to enhance our understanding of transcriptional regulation in hematopoiesis.
造血干细胞(HSCs)处于造血层级结构的顶端,具有自我更新以及向所有成熟血细胞谱系分化的能力。与更为特化的祖细胞一起,造血干细胞在维持健康的血液系统中发挥着至关重要的作用。干细胞/祖细胞中细胞命运决定的调控异常会导致成熟血细胞群体失衡——这种情况在白血病等疾病中可见。转录因子作为复杂调控网络的一部分,在调节造血细胞命运决定中发挥重要作用。然而,发现这些网络中存在的相互作用仍然是一个巨大的挑战。在此,我们讨论一种计算方法,该方法利用单细胞基因表达数据来重建布尔基因调控网络模型,并展示如何应用这项技术来增进我们对造血过程中转录调控的理解。