ObjectiveTo investigate the influence of Exo-1 gene deletion on the aging of the hematopoietic stem cell environmental defect of telomerase-deficient mice. Methods Recipients were the 3^rd generation telomerase knockout mice (G3 Terc-/-) or the 3^rd generation telomerase and Exo-1 gene double knockout mice (G3Terc-/-Exo-1-/-). Bone marrow cells were isolated from CD45.1 mice, and then injected into recipients at 2 month of age. Recipient mice were sacrificed at 9 month of age, the bone marrows, spleen, thymus and peripheral blood were collected and analyzed by flow cytometer. ResultsPercentage of B220⁺ cells increased in the wildtype donor derived bone marrow, spleen and peripheral blood cells in G3 Terc-/-Exo-1-/- double knockout recipient mice compared to those in G3Terc-/- recipient mice. Conclusion Exo-1 gene deletion rescued the hematopoietic stem cell environmental defect, and reversed the abnormal B cell development of hematopoietic stem cells.