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Regulation of lymphoid versus myeloid fate 'choice' by the transcription factor Mef2c

Nature Immunology volume 10, pages 289–296 (2009)Cite this article

Abstract

Despite advances in the identification of lymphoid-restricted progenitor cells, the transcription factors essential for their generation remain to be identified. Here we describe an unexpected function for the myeloid oncogene product Mef2c in lymphoid development. Mef2c deficiency was associated with profound defects in the production of B cells, T cells, natural killer cells and common lymphoid progenitor cells and an enhanced myeloid output. In multipotent progenitors, Mef2c was required for the proper expression of several key lymphoid regulators and restriction of the myeloid fate. Our studies also show that Mef2c was a critical transcriptional target of the transcription factor PU.1 during lymphopoiesis. Thus, Mef2c is a crucial component of the transcriptional network that regulates cell fate 'choice' in multipotent progenitors.

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Figure 1: Dynamic expression pattern of Mef2c during hematopoiesis.
Figure 2: Mef2c is essential for normal lymphoid development.
Figure 3: Mef2c is required at the level of the CLP.
Figure 4: Mef2c promotes a lymphoid fate for MPPs at the expense of a myeloid fate.
Figure 5: Antagonistic effect of Mef2c on myeloid differentiation.
Figure 6: Mef2c is a target of PU.1.

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Acknowledgements

We thank J. Schwartz (Albany Medical College) and Brian Black (University of California, San Francisco) for mutant mice; G. Bell and P. Thiru for microarray data analysis; members of the Jaenisch laboratory for discussions; R. Jimenez for mouse handling and technical support; and L. Lawton (Whitehead Institute for Biomedical Research) for reagents. Supported by the Whitehead Institute Fellows (F.D.C.) and the National Institutes of Health (AI052175 to R.P.D.).

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Authors and Affiliations

  1. Whitehead Institute for Biomedical Research, Cambridge, 02142, Massachusetts, USA

    Sandra Stehling-Sun & Fernando D Camargo

  2. Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, 45267, Ohio, USA

    Jessica Dade & Rodney P DeKoter

  3. The Walter and Eliza Hall Institute of Medical Research, Parkville, 3050, Victoria, Australia

    Stephen L Nutt

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  1. Sandra Stehling-Sun
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  3. Stephen L Nutt
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Contributions

S.S.-S. designed and did most of the experiments and wrote the manuscript; J.D. and R.P.D. did experiments relevant to PU.1 biology and provided intellectual input; S.L.N. provided critical reagents; and F.D.C. did experiments, designed and supervised research and wrote the manuscript.

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Correspondence to Fernando D Camargo.

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Stehling-Sun, S., Dade, J., Nutt, S. et al. Regulation of lymphoid versus myeloid fate 'choice' by the transcription factor Mef2c. Nat Immunol 10, 289–296 (2009). https://doi.org/10.1038/ni.1694

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