(a) Schematic of serial FL transplantation experimental design. (b) Peripheral blood and LKS analysis of FL transplant recipients 16 weeks after transplant revealed peripheral leukopenia (WBC) and specifically B cell (B220+) lymphopenia in the absence of Tle4 with no difference in LKS, LKS, CD34+, LKS CD34− populations (n = 10 per genotype for blood analysis, n = 6–7 per genotype for LKS analysis, ***: P<.0001). (c) Peripheral blood and LKS analysis 16 weeks after secondary transplantation also indicates leukopenia and lymphopenia in Tle4 null cells, but at this time also a significant decrease in LKS and LKS, CD34− populations (n = 5 KO recipients, n = 10 WT recipients for blood analysis, n = 5 mice per group for LKS analysis, *: P<.05 **: P<.001). (d) Peripheral blood analysis and LKS analysis 16 weeks after tertiary transplantation again showed leukopenia, B-cell lymphopenia, and a profound decrease in all HSC containing populations (n = 4 per genotype for blood and LKS analysis, *: P<.05, **: P<.01, ***: P<.001). (e) Representative flow cytometry plots showing progressive loss of Tle4 null HSCs over successive transplantation.