TY - JOUR
T1 - Bcl-2 and Bcl-XL are indispensable for the late phase of mast cell development from mouse embryonic stem cells
AU - Möller, Christine
AU - Karlberg, Mats
AU - Åbrink, Magnus
AU - Nakayama, Keiichi I.
AU - Motoyama, Noboru
AU - Nilsson, Gunnar
N1 - Funding Information:
We would like to thank Uppsala University Transgenic Facility for the help in growing ES cells. This study was supported by grants from the Swedish Research Council-Medicine, the Swedish Cancer Foundation, the Swedish Cancer and Allergy Fund, Consul Th C Berg's Foundation, Ollie and Elof Ericsson's Foundation, King Gustaf V's 80-Years Foundation, Ellen, Walter and Lennart Hesselman's Foundation, Swedish Animal Welfare Agency, and Karolinska Institutet.
PY - 2007/3
Y1 - 2007/3
N2 - Objective: The aim of this study was to determine the importance of the prosurvival factors Bcl-2 and Bcl-XL for mast cell development and survival. Methods: bcl-x-/- and bcl-2-/- mouse embryonic stem cells were maintained in medium supplemented with either interleukin (IL)-3 or IL-3 in combination with stem cell factor (SCF) to favor mast cell development. The development of Bcl-2 family deficient embryonic stem cell-derived mast cells (ESMCs) was monitored and Bcl-2 family gene expression and cell numbers were analyzed. Results: Deficiency in either bcl-x or bcl-2 totally inhibited the development of ESMCs when IL-3 alone was used as a mast cell growth factor. Intriguingly, when IL-3 was used in combination with SCF, the ESMCs developed normally the first 2 weeks but thereafter the cell numbers dropped drastically. The remaining ESMCs express mouse mast cell protease 1, suggesting a mucosal-like phenotype. ESMCs lacking bcl-x or bcl-2 exhibited strong expression of A1, another prosurvival Bcl-2 family member. Conclusion: For the first time we provide direct evidence that both bcl-x and bcl-2 are indispensable for mast cell survival during the late phase of their development.
AB - Objective: The aim of this study was to determine the importance of the prosurvival factors Bcl-2 and Bcl-XL for mast cell development and survival. Methods: bcl-x-/- and bcl-2-/- mouse embryonic stem cells were maintained in medium supplemented with either interleukin (IL)-3 or IL-3 in combination with stem cell factor (SCF) to favor mast cell development. The development of Bcl-2 family deficient embryonic stem cell-derived mast cells (ESMCs) was monitored and Bcl-2 family gene expression and cell numbers were analyzed. Results: Deficiency in either bcl-x or bcl-2 totally inhibited the development of ESMCs when IL-3 alone was used as a mast cell growth factor. Intriguingly, when IL-3 was used in combination with SCF, the ESMCs developed normally the first 2 weeks but thereafter the cell numbers dropped drastically. The remaining ESMCs express mouse mast cell protease 1, suggesting a mucosal-like phenotype. ESMCs lacking bcl-x or bcl-2 exhibited strong expression of A1, another prosurvival Bcl-2 family member. Conclusion: For the first time we provide direct evidence that both bcl-x and bcl-2 are indispensable for mast cell survival during the late phase of their development.
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U2 - 10.1016/j.exphem.2006.11.008
DO - 10.1016/j.exphem.2006.11.008
M3 - Article
C2 - 17309819
AN - SCOPUS:33847069199
SN - 0301-472X
VL - 35
SP - 385
EP - 393
JO - Experimental Hematology
JF - Experimental Hematology
IS - 3
ER -
