Analysis of the bone marrow compartments between young and old mice show significant cellular and transcriptomic differences. (A) Age-associated differences of the hematopoietic bone marrow compartments from young and old mice (n = 5 mice per group; mean plus or minus SEM). (B) Old mice exhibit higher numbers of megakaryocyte (MK)-committed progenitors (MkPs) (n = 5 mice per group; mean plus or minus SEM). (C) Megakaryocyte ploidy analysis of bone marrow megakaryocytes from young and old mice (n = 5 mice per group; mean plus or minus SEM). (D) scRNA-seq of native bone marrow megakaryocytes from young and old mice (n = 4-5 mice per group) identifies 7 clusters of cells at different maturation stages. (E) Identification of megakaryocyte maturation regions (MK regions 1-7) based on megakaryocyte-specific transcripts. (F) Representative heat map of the mitochondrial dysfunction IPA gene pathway across the 7 megakaryocyte regions. (G) IPA identifies significant differentially regulated mitochondrial, metabolic, and inflammatory gene pathways in the transcriptome of young and old bone marrow megakaryocytes. *P < .05; **P < .01; and ***P < .001. Two-tailed t test and Mann-Whitney test. LT-HSC, long-term hematopoietic stem cell; fMLP, N-Formylmethionyl-leucyl-phenylalanine; ST-HSC, short-term hematopoietic stem cell.