Inflammatory signals from fatty bone marrow support DNMT3A driven clonal hematopoiesis.

ABSTRACT: Both fatty bone marrow (FBM) and somatic mutations in hematopoietic stem cells (HSCs), also termed clonal hematopoiesis (CH) accumulate with human aging. However it remains unclear whether FBM can modify the evolution of CH. To address this question, we herein present the interaction between CH and FBM in two preclinical male mouse models: after sub-lethal irradiation or after castration. An adipogenesis inhibitor (PPARγ inhibitor) is used in both models as a control. A significant increase in self-renewal can be detected in both human and rodent DNMT3A^Mut-HSCs when exposed to FBM. DNMT3A^Mut-HSCs derived from older mice interacting with FBM have even higher self-renewal in comparison to DNMT3A^Mut-HSCs derived from younger mice. Single cell RNA-sequencing on

SUBMITTER: Zioni N 

PROVIDER: S-EPMC10097668 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature