OBJECTIVE: Hematopoietic regeneration is regulated by cell survival proteins, such as the Bcl-2 family. Bid, a BH3-only protein of the Bcl-2 family, has multiple cellular functions and is involved in a variety of physiological or pathological conditions. We attempted to define its role in hematopoietic cell repopulation under the stress condition of bone marrow transplantation. MATERIALS AND METHODS: We performed conventional or competitive bone marrow transplantation with donor hematopoietic cells from Bid(-/-) or Bid(+/+) mice. Flow cytometry was used for quantification of hematopoietic stem cells, hematopoietic progenitor cells, and differentiated cells in different lineages (T, B, and myeloid cells). Single cell culture and homing assays were performed to further evaluate hematopoietic stem cell functions. Hematopoietic progenitor cells were also measured by the colony-forming cell culture. RESULTS: Contrary to the widely recognized role of Bid as a pro-apoptotic protein, the absence of Bid significantly reduced the reconstitution of donor hematopoietic cells in γ-irradiated recipients. Interestingly, however, numbers of hematopoietic stem cells and hematopoietic progenitor cells and their functions were not overtly altered. Instead, the regeneration of donor T and B cells was significantly impaired in the absence of Bid. Further analysis indicated an accumulation of the triple-negative T-cell population in the thymus, and pro-B cells in the bone marrow. CONCLUSIONS: Our current study demonstrates a positive impact of Bid on hematopoietic regeneration mainly due to its unique effects on donor lymphopoiesis in the transplant recipients.
OBJECTIVE: Hematopoietic regeneration is regulated by cell survival proteins, such as the Bcl-2 family. Bid, a BH3-only protein of the Bcl-2 family, has multiple cellular functions and is involved in a variety of physiological or pathological conditions. We attempted to define its role in hematopoietic cell repopulation under the stress condition of bone marrow transplantation. MATERIALS AND METHODS: We performed conventional or competitive bone marrow transplantation with donor hematopoietic cells from Bid(-/-) or Bid(+/+) mice. Flow cytometry was used for quantification of hematopoietic stem cells, hematopoietic progenitor cells, and differentiated cells in different lineages (T, B, and myeloid cells). Single cell culture and homing assays were performed to further evaluate hematopoietic stem cell functions. Hematopoietic progenitor cells were also measured by the colony-forming cell culture. RESULTS: Contrary to the widely recognized role of Bid as a pro-apoptotic protein, the absence of Bid significantly reduced the reconstitution of donor hematopoietic cells in γ-irradiated recipients. Interestingly, however, numbers of hematopoietic stem cells and hematopoietic progenitor cells and their functions were not overtly altered. Instead, the regeneration of donor T and B cells was significantly impaired in the absence of Bid. Further analysis indicated an accumulation of the triple-negative T-cell population in the thymus, and pro-B cells in the bone marrow. CONCLUSIONS: Our current study demonstrates a positive impact of Bid on hematopoietic regeneration mainly due to its unique effects on donor lymphopoiesis in the transplant recipients.
Authors: N Plesnila; S Zinkel; D A Le; S Amin-Hanjani; Y Wu; J Qiu; A Chiarugi; S S Thomas; D S Kohane; S J Korsmeyer; M A Moskowitz Journal: Proc Natl Acad Sci U S A Date: 2001-12-11 Impact factor: 11.205
Authors: V Stoka; B Turk; S L Schendel; T H Kim; T Cirman; S J Snipas; L M Ellerby; D Bredesen; H Freeze; M Abrahamson; D Bromme; S Krajewski; J C Reed; X M Yin; V Turk; G S Salvesen Journal: J Biol Chem Date: 2000-11-09 Impact factor: 5.157
Authors: V R Sutton; J E Davis; M Cancilla; R W Johnstone; A A Ruefli; K Sedelies; K A Browne; J A Trapani Journal: J Exp Med Date: 2000-11-20 Impact factor: 14.307
Authors: Jingang Gui; Amanda J Morales; Sophie E Maxey; Katherine A Bessette; Nora R Ratcliffe; John A Kelly; Ruth W Craig Journal: Int Immunol Date: 2011-09-21 Impact factor: 4.823