Signatures of murine B-cell development implicate Yy1 as a regulator of the germinal center-specific program

Michael R. Green, Stefano Monti, Riccardo Dalla-Favera, Laura Pasqualucci, Nicole C. Walsh, Marc Schmidt-Supprian, Jeffery L. Kutok, Scott J. Rodig, Donna S. Neuberg, Klaus Rajewsky, Todd R. Golub, Frederick W. Alt, Margaret A. Shipp, John P. Manis

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37 Scopus citations

Abstract

We utilized gene expression profiling of a comprehensive panel of purified developmentally defined normal murine B cells to identify unique transcriptional signatures for each subset. To elucidate transcription factor activities that function in a stage-specific fashion, we used gene sets that share transcription factor targets and found that germinal center B cells had a robust enrichment of up-regulated and down-regulated signatures compared with the other B-cell subsets. Notably, we found Yy1 and its targets to be central regulators of the germinal center B (GCB)-specific transcriptional program with binding of Yy1 to select signature genes in GCB cells, and translation of the Yy1 signatures to human GCB cells. We then tested whether our newly generated, stage-specific transcriptional signatures could be used to link murine lymphoma models to stages of normal B-cell development. Although each of the molecularly defined murine lymphoma models conserved certain stage-specific features of normal B-cell development, there was a significant alteration of the normal differentiation signature following malignant transformation. These findings offer important tools and insights for elucidating differences between normal and malignant B cells.

Original languageEnglish (US)
Pages (from-to)2873-2878
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number7
DOIs
StatePublished - Feb 15 2011
Externally publishedYes

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    Green, M. R., Monti, S., Dalla-Favera, R., Pasqualucci, L., Walsh, N. C., Schmidt-Supprian, M., Kutok, J. L., Rodig, S. J., Neuberg, D. S., Rajewsky, K., Golub, T. R., Alt, F. W., Shipp, M. A., & Manis, J. P. (2011). Signatures of murine B-cell development implicate Yy1 as a regulator of the germinal center-specific program. Proceedings of the National Academy of Sciences of the United States of America, 108(7), 2873-2878. https://doi.org/10.1073/pnas.1019537108