Fig. 3: Enhanced mitochondrial respiration in transplanted Dnmt3aR882H/+.
From: Mitochondrial metabolism sustains DNMT3A-R882-mutant clonal haematopoiesis
a,b, Proliferation of Dnmt3aR882H/+ (a) and WT (b) HSPCs after editing of the indicated gene. The BFP-positive fraction was compared with the non-transduced population and normalized to day 4 and Empty vector for each gRNA. For a and b, the mean ± s.d. is shown; n = 3 biological replicates for Kdm1a gRNA and n = 4 biological replicates for the remining gRNAs in Dnmt3aR882H/+. n = 4 biological replicates for Mlst8, Jak1, Brd2 gRNAs and n = 6 biological replicates for the remining gRNAs in WT. Asterisk indicates significant depletion in Dnmt3aR882H/+ versus WT HSPCs calculated for each day. P by two-sided t-test. c, Schematic representation of the experimental setup for mitochondrial respiration analysis of WT and Dnmt3aR882H/+ HSPCs extracted eight weeks post-transplantation performed with the Seahorse analyser. d, Example of OCR in transplanted WT and Dnmt3aR882H/+ HSPCs, measured using a Seahorse extracellular flux analyser; mean ± s.e.m. n = 18 for Dnmt3aR882H/+, n = 15 for WT representing three independent biological replicates, for each Dnmt3aR882H/+ performed in six replicates, for WT performed in four, five and six replicates respectively. R + A indicates rotenone and antimycin A. e, Basal respiration, maximal respiration, ATP production and spare respiration capacity were calculated; mean ± s.d. P by two-sided t-test. n = 3 biological replicates per genotype. Similar results were obtained when Dnmt3aR882H/+ versus WT cells were transplanted separately into recipients (Extended Data Fig. 4g–i). *Higher depletion in Dnmt3aR882H/+ versus WT. d, day. Schematic in c was created using BioRender (https://biorender.com). Seahorse picture in c adapted with permission from K. Gozdecki.
