Extended Data Fig. 7: Adiponectin-creER; Ngf fl/∆ mice exhibit defects in nerve fiber sprouting and hematopoietic and vascular regeneration after irradiation.
(a) The area occupied by peripherin+ nerve fibers in bone marrow sections from 2-3 month-old Adiponectin-creER; Ngf fl/∆ and Ngf fl/∆ littermate controls before, or 28 days after irradiation and transplantation (7 mice per genotype per time point from 7 independent experiments). (b-d) Cellularity (b), numbers of HSCs (c) and LSK cells (d) in bone marrow (one tibia and one femur) from Adiponectin-creER; Ngf fl/∆ and littermate control mice before and 28 days after irradiation and transplantation. (e) Leakage of intravenously-injected Evans blue dye into femur bone marrow at the indicated time points after irradiation and bone marrow transplantation. (f, g) Numbers of LepR+ cells (f) and endothelial cells (g) in the bone marrow before, or 14 or 28 days after irradiation and bone marrow transplantation (5 mice per genotype from 5 independent experiments in panels b-g). (h - j) SCF (h), VEGF (i) and Ang2 (j) in bone marrow serum from 2-3 month-old Adiponectin-creER; Ngf fl/∆ and littermate control mice before, or 14 or 28 days after irradiation and transplantation (a total of 8 mice per genotype per time point from 8 independent experiments). (k-o) When administered to Leprcre/+; Ngf fl/∆ mice after irradiation, the b2 agonist salbutamol rescued the regeneration of bone marrow LepR+ cells (k) and endothelial cells (l) at 28 days after irradiation, as well as bone marrow SCF (m), VEGF (n), and Ang2 (o) levels 14 days after irradiation (6 mice per genotype per treatment from 6 independent experiments). All data represent mean ± standard deviation. Statistical significance was assessed using matched samples two-way ANOVAs followed by the Tukey’s (a, h, and i) or Sidak’s (b, d, f, and k-o) multiple comparisons adjustment, Student’s t-tests (c, e, and g) or Mann-Whitney tests (for genotype comparisons of j) followed by the Holm-Sidak’s multiple comparisons adjustment, or Friedman tests followed by the Dunn’s multiple comparisons adjustment (for time-point comparisons of j). All statistical tests were two-sided. Not significant (NS): P > 0.05.
