Progressive erosion of the HSC self-renewal potential in obesity. (A) Scheme showing the phenotypic definition of HSC subsets in the HSC-SLAM compartment. IT, intermediate term; LT, long term; ST, short term. (B) Mean percentage ± standard deviation (SD) of HSC subsets (defined by CD34 and CD49b expression) that composed the HSC-SLAM compartment in the bone marrow (BM) of 4-month-old control (Ctrl) and db mice (n = 3). (C) Experimental scheme used to functionally test HSC subsets in a serial transplantation assay. (D-E) Serial competitive transplantation assays in nonlimiting conditions for HSC^CD49b– (upper panels), HSC^CD49b+ (central panels) and MPP1 (lower panels) subsets isolated from the BM of 4-month-old control and db mice. Hematopoietic reconstitution in primary (D) and secondary (E) recipients. Graphs indicate peripheral blood (PB) chimerism over time (left) and BM chimerism for HSC subsets 20 weeks after transplantation (right). Results from 2 independent experiments are expressed as means ± SD (n = 9-14 for primary and n = 5-11 for secondary transplantation). (F) Competitive transplantation assay for HSC^CD49b– subsets in limiting condition (50 cells per recipient). Graphs indicate PB chimerism over time (n = 9-11). Results from 2 independent experiments are expressed as means ± SD. Two-way ANOVA with Sidak’s post hoc test; *P ≤ .05; **P ≤ .01; ***P ≤ .005.