NEIL3-deficient bone marrow displays decreased hematopoietic capacity and reduced telomere length

Deficiency of NEIL3, a DNA repair enzyme, has significant impact on mouse physiology, including vascular biology and gut health, processes related to aging. Leukocyte telomere length (LTL) is suggested as a marker of biological aging, and shortened LTL is associated with increased risk of cardiovascular disease. NEIL3 has been shown to repair DNA damage in telomere regions in vitro. Herein, we explored the role of NEIL3 in telomere maintenance in vivo by studying bone marrow cells from atherosclerosis-prone NEIL3-deficient mice. We found shortened telomeres and decreased activity of the telomerase enzyme in bone marrow cells derived from Apoe(−/−)Neil3(−/−) as compared to Apoe(−/−) mice. Furthermore, Apoe(−/−)Neil3(−/−) mice had decreased leukocyte levels as compared to Apoe(−/−) mice, both in bone marrow and in peripheral blood. Finally, RNA sequencing of bone marrow cells from Apoe(−/−)Neil3(−/−) and Apoe(−/−) mice revealed different expression levels of genes involved in cell cycle regulation, cellular senescence and telomere protection. This study points to NEIL3 as a telomere-protecting protein in murine bone marrow in vivo.