Abstract
Large quantities of highly enriched populations of mast cells can be generated from mouse embryonic stem (ES) cells using an in vitro differentiation system. These embryonic stem cell-derived mast cells (ESMCs) exhibit many similarities to mouse bone marrow-derived cultured mast cells (BMCMCs), including the abilities to survive and to orchestrate immunologically specific immunoglobulin E (IgE)-dependent reactions in vivo after transplantation into genetically mast cell—deficient KitW/KitW-v mice. Coupled with the current spectrum of techniques for genetically manipulating ES cells, ESMCs represent a unique model system to analyze the effects of specific alterations in gene structure, expression, or function, including embryonic lethal mutations, on mast cell development, phenotype, and function in vitro and in vivo.
Similar content being viewed by others
References
Evans MJ, Kaufman MH. Establishment in culture of pluripotent cells from mouse embryos.Nature. 1981;292:154–156.
Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma cell.Proc Natl Acad Sci U S A. 1981;78:7634–7638.
Robertson EJ. Pluripotential stem cell lines as a route into the mouse germ line.Trends Genet. 1986;2:9–13.
Keller G. In vitro differentiation of embryonic stem cells.Curr Opin Cell Biol. 1995;7:862–869.
Weiss MJ, Orkin SH. In vitro differentiation of murine embryonic stem cells.J Clin Invest. 1996;97:591–595.
Galli SJ. Mast cells and basophils.Curr Opin Hematol. 2000;7: 32–39.
Galli SJ, Wedemeyer J, Tsai M. Analyzing the roles of mast cells and basophils in host defense and other biological responses.Int J Hematol. 2002;75:363–369.
Kitamura Y. Heterogeneity of mast cells and phenotypic changes between subpopulations.Annu Rev Immunol. 1989;7:59–76.
Galli SJ, Geissler EN, Wershil BK, Gordon JR, Tsai M, Hammel I. Insights into mast cell development and function derived from analyses of mice carrying mutations atBeige,W/c-kit, orSl/SCF (c- kit Ligand) loci. In: Kaliner MA, Metcalfe DD, eds.The Mast Cell in Health and Disease. New York, NY: Marcel Dekker; 1993:129–201.
Wiles MV, Keller G. Multiple hematopoietic lineages develop from embryonic stem (ES) cells in culture.Development. 1991;111: 259–267.
Keller G, Kennedy M, Papayannopoulou T, Wiles MV. Hematopoietic commitment during embryonic stem cell differentiation in culture.Mol Cell Biol. 1993;13:473–486.
Tsai M, Wedemeyer J, Ganiatsas S, Tam S-Y, Zon LI, Galli SJ. Generation and characterization of mast cells derived from mouse embryonic stem cells: a method to analyze the effects of “lethal mutations” in adult mice in vivo. Abstract 337, presented at the Keystone Symposium: Stem Cells, Asymmetric Cell Division and Cell Fate; Feb., 2000; Keystone, Co. USA.
Tsai M, Wedemeyer J, Ganiatsas S, Tam S-Y, Zon LI, Galli SJ. In vivo immunological function of mast cells derived from embryonic stem cells: an approach for the rapid analysis of even embryonic lethal mutations in adult mice in vivo.Proc Natl Acad Sci U S A. 2000;97:9186–9190.
Garrington TP, Ishizuka T, Papst PJ, et al. MEKK2 gene disruption causes loss of cytokine production in response to IgE and c-Kit ligand stimulation of ES cell-derived mast cells.EMBO J. 2000;19: 5387–5395.
Tsai F-Y, Keller G, Kuo FC, et al. An early hematopoietic defect in mice lacking the transcription factor GATA-2.Nature. 1994;371: 221–226.
Zmuidzinas A, Fischer K-D, Lira SA, et al. Thevav proto-oncogene is required early in embryogenesis but not for hematopoietic development in vitro.EMBO J. 1995;14:1–11.
Ganiatsas S, Kwee L, Fujiwara Y, et al. SEK1 deficiency reveals mitogen-activated protein kinase cascade crossregulation and leads to abnormal hepatogenesis.Proc Natl Acad Sci U S A. 1998; 95:6881–6886.
Tsai F-Y, Orkin SH. Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation.Blood. 1997;89:3636–3643.
Keller G, Snodgrass HR. Human embryonic stem cells: the future is now.Nature Med. 1999;5:151–152.
Lee SH,Lumelsky N,Studer L,Auerbach JM, McKay RD. Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells.Nat Biotechnol. 2000;18:675–679.
Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, McKay R. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets.Science. 2001;292:1389–1394.
Author information
Authors and Affiliations
About this article
Cite this article
Tsai, M., Tam, SY., Wedemeyer, J. et al. Mast Cells Derived from Embryonic Stem Cells: A Model System for Studying the Effects of Genetic Manipulations on Mast Cell Development, Phenotype, and Function In Vitro and In Vivo. Int J Hematol 75, 345–349 (2002). https://doi.org/10.1007/BF02982122
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF02982122