Nucleic acid-induced inflammation on hematopoietic stem cells

Abstract

Hematopoiesis, the process of generating blood cells, starts during development with the primitive, pro-definitive, and definitive hematopoietic waves. The first two waves will generate erythrocytes and myeloid cells, although the definitive wave will give rise to hematopoietic stem cells (HSCs) that are multipotent and can produce most of the blood cells in an adult. Although HSCs are highly proliferative during development, during adulthood they remain quiescent in the bone marrow. Inflammatory signaling in the form of interferons, interleukins, tumor necrosis factors, and others is well-established to influence both developmental and adult hematopoiesis. Here we discuss the role of specific inflammatory pathways that are induced by sensing nucleic acids. We discuss the role of RNA-sensing members of the Toll-like, Rig-I-like, nucleotide-binding oligomerization domain (NOD)-like, and AIM2-like protein kinase receptors and the DNA-sensing receptors, DEAD-Box helicase 41 (DDX41) and cGAS. The main downstream pathways of these receptors are discussed, as well as their influence on developmental and adult hematopoiesis, including hematopoietic pathologies.