Bcl-2 and Bcl-XL are indispensable for the late phase of mast cell development from mouse embryonic stem cells
2007 (English)In: Experimental Hematology, ISSN 0301-472X, E-ISSN 1873-2399, Vol. 35, no 3, 385-393 p.Article in journal (Refereed) Published
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 Al, 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.
Place, publisher, year, edition, pages
2007. Vol. 35, no 3, 385-393 p.
Animals, Cell Differentiation/drug effects/physiology, Cell Proliferation/drug effects, Cell Survival/drug effects/physiology, Cells; Cultured, Gene Expression Profiling, Genotype, Interleukin-3/pharmacology, Mast Cells/*cytology/drug effects/*metabolism, Mice, Mice; Knockout, Proto-Oncogene Proteins/genetics/*physiology, Proto-Oncogene Proteins c-bcl-2/genetics, RNA; Messenger/genetics, Reverse Transcriptase Polymerase Chain Reaction, Stem Cell Factor/pharmacology, Stem Cells/*cytology/drug effects/*metabolism, bcl-X Protein/genetics/*physiology
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-15816DOI: 10.1016/j.exphem.2006.11.008PubMedID: 17309819OAI: oai:DiVA.org:uu-15816DiVA: diva2:43587