Abstract：
The emergence of multiomic single-cell technologies over the last decade has led to improved insights into both normal hematopoiesis and its perturbation in a variety of hematological disorders. Diamond-Blackfan anemia (DBA) syndrome is one such disorder where single-cell assays have helped to delineate the cellular and molecular defects underlying the disease. DBA is caused by heterozygous loss-of-function germline variants in genes encoding ribosomal proteins (RPs). Despite the widespread role of ribosomes in hematopoiesis, the most frequent and severe cytopenia in DBA is anemia. In this review we discussed how single-cell studies, including clonogenic cell culture assays, fluorescence-activated cell sorting (FACS) and single-cell RNA sequencing (scRNA-seq), have led to insights into the pathogenesis of DBA. The main therapies are regular blood transfusions, glucocorticoids, or hematopoietic stem cell transplantation (HSCT) but all are associated with significant morbidity and mortality. We will therefore outline how single-cell studies can inform new therapies for DBA. Furthermore, we discussed how DBA serves as a useful model for understanding normal erythropoiesis in terms of its cellular hierarchy, molecular regulation during homeostasis, and response to \"stress.\"
摘要：
在过去的十年中，多种单细胞技术的出现导致对正常造血功能及其在各种血液系统疾病中的扰动的认识得到了改善。Diamond-Blackfan贫血（DBA）就是这样一种疾病，其中单细胞分析有助于描绘该疾病背后的细胞和分子缺陷。DBA是由编码核糖体蛋白（RP）的基因中功能种系变体的杂合缺失引起的。尽管核糖体在造血中具有广泛的作用，DBA中最常见和最严重的血细胞减少是贫血.在这篇综述中，我们将讨论单细胞研究-包括克隆细胞培养试验，荧光激活细胞分选（FACS）和单细胞RNA测序（scRNAseq）-已导致对DBA发病机理的见解。主要的治疗方法是定期输血,糖皮质激素或造血干细胞移植（HSCT），但都与显着的发病率和死亡率有关。因此，我们将概述单细胞研究如何为DBA提供新疗法。此外，我们将讨论DBA如何作为一个有用的模型来理解正常的红细胞生成，分子调节过程中的稳态和对压力的反应。
