Next Generation Sequencing Facilitates Quantitative Analysis of the Role of Ddx21 in hematopoietic stem cells [RNA-seq]

DDX21, a nucleolus-localized DEAD-box RNA helicase, serves as a master regulator in ribosomal DNA (rDNA) transcription and ribosome assembly. Nevertheless, its precise function in adult hematopoiesis remains incompletely understood.

Here, we reveal that conditional knockout of Ddx21 in the murine hematopoietic system triggers collapse of HSC homeostasis, characterized by loss of quiescence, impaired self-renewal capacity, and raised apoptosis. Mechanistically, we demonstrate that DDX21 physically associates with both rDNA loci and promoters of ribosomal protein genes. Its loss disrupts ribosome production, causes nucleolar stress, culminates in p53-mediated cell cycle arrest and apoptosis in HSPCs.