Department of Cell and Regenerative Biology, Wisconsin Blood Cancer Research Institute, Wisconsin Institutes for Medical Research, University of Wisconsin School of Medicine and Public Health, Carbone Cancer Center, Madison, WI; Cellular and Molecular Biology Graduate Program, University of Wisconsin School of Medicine and Public Health, Madison, WI.
Department of Cell and Regenerative Biology, Wisconsin Blood Cancer Research Institute, Wisconsin Institutes for Medical Research, University of Wisconsin School of Medicine and Public Health, Carbone Cancer Center, Madison, WI.
Exp Hematol. 2024 Mar;131:104167. doi: 10.1016/j.exphem.2024.104167. Epub 2024 Jan 21.
Every second, the body produces 2 million red blood cells through a process called erythropoiesis. Erythropoiesis is hierarchical in that it results from a series of cell fate decisions whereby hematopoietic stem cells progress toward the erythroid lineage. Single-cell transcriptomic and proteomic approaches have revolutionized the way we understand erythropoiesis, revealing it to be a gradual process that underlies a progressive restriction of fate potential driven by quantitative changes in lineage-specifying transcription factors. Despite these major advances, we still know very little about what cell fate decision entails at the molecular level. Novel approaches that simultaneously measure additional properties in single cells, including chromatin accessibility, transcription factor binding, and/or cell surface proteins are being developed at a fast pace, providing the means to exciting new advances in the near future. In this review, we briefly summarize the main findings obtained from single-cell studies of erythropoiesis, highlight outstanding questions, and suggest recent technological advances to address them.
人体每秒钟通过一个称为红细胞生成的过程产生 200 万个红细胞。红细胞生成是分层次的,它是由一系列细胞命运决定的结果,造血干细胞朝着红细胞谱系前进。单细胞转录组学和蛋白质组学方法彻底改变了我们对红细胞生成的理解,揭示它是一个渐进的过程,其基础是由谱系特异性转录因子的定量变化驱动的命运潜力的逐渐限制。尽管取得了这些重大进展,但我们对分子水平上的细胞命运决定仍知之甚少。同时测量单细胞中其他特性(包括染色质可及性、转录因子结合和/或细胞表面蛋白)的新方法正在快速发展,为未来的激动人心的新进展提供了手段。在这篇综述中,我们简要总结了从红细胞生成的单细胞研究中获得的主要发现,强调了悬而未决的问题,并提出了最近的技术进展来解决这些问题。