Bcl-2 and Bcl-XL are indispensable for the late phase of mast cell development from mouse embryonic stem cells

Möller, Christine; Karlberg, Mats; Åbrink, Magnus; Nakayama, Keiichi I.; Motoyama, Noboru; Nilsson, Gunnar

doi:10.1016/j.exphem.2006.11.008

« Previous Next »Experimental Hematology
Volume 35, Issue 3 , Pages 385-393, March 2007

Bcl-2 and Bcl-XL are indispensable for the late phase of mast cell development from mouse embryonic stem cells

Christine Möller
- Department of Medicine, Karolinska Institutet, Stockholm, Sweden
- Offprint requests to: Christine Möller, Ph.D., Karolinska Institutet, Department of Medicine, Clinical Immunology and Allergy Unit, KS L2:04, SE-171 76 Stockholm, Sweden
Mats Karlberg
- Department of Medicine, Karolinska Institutet, Stockholm, Sweden
Magnus Åbrink
- Department of Molecular Biosciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
Keiichi I. Nakayama
- Division of Cell Biology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
Noboru Motoyama
- Department of Geriatric Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan
Gunnar Nilsson
- Department of Medicine, Karolinska Institutet, Stockholm, Sweden

Received 3 May 2006; received in revised form 16 November 2006; accepted 16 November 2006.

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.