Interlukin-4 weakens resistance to stress injury and megakaryocytic differentiation of hematopoietic stem cells by inhibiting Psmd13 expression.

ABSTRACT: Thrombocytopenia is a major and fatal complication in patients with acute myeloid leukemia (AML), which results from disrupted megakaryopoiesis by leukemic niche and blasts. Our previous research revealed that elevated interleukin-4 (IL-4) in AML bone marrow had adverse impact on multiple stages throughout megakaryopoiesis including hematopoietic stem cells (HSCs), but the specific mechanism remains unknown. In the present study, we performed single-cell transcriptome analysis and discovered activated oxidative stress pathway and apoptosis pathway in IL-4Rα^high versus IL-4Rα^low HSCs. IL-4 stimulation in vitro led to apoptosis of HSCs and down-regulation of megakaryocyte-associated transcription factors. Functional assays displayed higher susceptibility of IL-4Rα^h

SUBMITTER: Gao A 

PROVIDER: S-EPMC10471741 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature