Tamura Tomohiko, Kurotaki Daisuke
Department of Immunology, Yokohama City University Graduate School of Medicine.
Advanced Medical Research Center, Yokohama City University.
Rinsho Ketsueki. 2019;60(9):1075-1083. doi: 10.11406/rinketsu.60.1075.
The mechanism underlying production of various types of blood cells from hematopoietic stem and progenitor cells has been a central theme in hematology. Conventionally, hematopoietic cell populations are analyzed by cell surface markers to judge cell types and differentiation stages, and by transplantation assays to assess differentiation potential. Recently, however, next-generation sequencing technology has enabled single-cell transcriptome and epigenome analyses and cell barcoding-based lineage tracing during unperturbed hematopoiesis. These innovative assays revealed that each cell population is extensively heterogenous. Many cells within hematopoietic stem cell populations may not be multipotent, and conversely, hematopoietic progenitor cells often display self-renewal capacity. Moreover, cells tend to make their lineage choice much earlier than previously thought. Altogether, these results challenge the current hierarchical differentiation models and propose new continuous models. Single-cell analyses are expected to greatly contribute to our understanding of normal and abnormal hematopoiesis and to the development of new therapies for blood disorders.
造血干细胞和祖细胞产生各类血细胞的机制一直是血液学的核心主题。传统上，通过细胞表面标志物分析造血细胞群体以判断细胞类型和分化阶段，并通过移植试验评估分化潜能。然而，近年来，新一代测序技术已能够在未受干扰的造血过程中进行单细胞转录组和表观基因组分析以及基于细胞条形码的谱系追踪。这些创新性试验揭示了每个细胞群体都具有广泛的异质性。造血干细胞群体中的许多细胞可能并非多能性的，相反，造血祖细胞常常表现出自我更新能力。此外，细胞做出谱系选择的时间往往比之前认为的要早得多。总之，这些结果对当前的层级分化模型提出了挑战，并提出了新的连续模型。单细胞分析有望极大地增进我们对正常和异常造血的理解，并推动血液疾病新疗法的开发。
