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Single cell transcriptome profiling of Reticular Dysgenesis patient bone marrow

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE179346 | GEO | 2021/07/06

REPOSITORIES: GEO

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Project description: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). To study the effect of AK2 depletion on HSPC differentiation, we developed a biallelic AK2 CRISPR knock-out model using human HSPCs. AK2 depleted HSPCs display severe proliferation and myeloid differentiation defects, recapitulating RD patient phenotype.

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