Single cell transcriptome profiling of Reticular Dysgenesis patient bone marrow

Reticular Dysgenesis (RD) is a rare but devastating form of severe combined immunodeficiency, characterized by a maturation arrest of the myeloid and lymphoid lineages paired with sensorineural hearing loss. RD is caused by biallelic loss-of-function mutations in the mitochondrial enzyme adenylate kinase 2 (AK2). Understanding the gene expression impact of AK2 loss-of-function on a single cell level would not only allow us to develop rational therapies for RD and other mitochondrial diseases but enable us to reconstruct metabolic changes that occur during development and how they impact cell fate decisions. Overall design: Single cell RNA-seq of CD45+ bone marrow cells from RD patients and a healthy donor.

网状组织发育不全（Reticular Dysgenesis, RD）是一种罕见却极具破坏性的重症联合免疫缺陷病症，以髓系与淋巴系细胞谱系成熟停滞并伴随感音神经性听力损失为典型特征。该疾病由线粒体酶腺苷酸激酶2（adenylate kinase 2, AK2）的双等位基因功能丧失突变引发。阐明AK2功能丧失在单细胞水平对基因表达的影响，不仅可为开发RD及其他线粒体疾病的针对性治疗方案提供理论支撑，还能帮助我们重构发育过程中发生的代谢变化，以及此类变化对细胞命运决定的调控机制。实验设计概述：对RD患者与健康供者的CD45阳性骨髓细胞开展单细胞RNA测序（Single cell RNA-seq）。