Transkriptionelle Kontrolle der B-Zellplastizität und Onkogenese durch Pax5 Meinrad Busslinger Institut für Molekulare Pathologie, Wien.

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 Präsentation transkript:

Transkriptionelle Kontrolle der B-Zellplastizität und Onkogenese durch Pax5 Meinrad Busslinger Institut für Molekulare Pathologie, Wien

Transkriptionsfaktoren kontrollieren die Genexpression Pax5

B-Zelldifferenzierung Pax5 definiert die Identität der B-Zelle

Deletion of the Pax5 gene in mature B cells conditional Pax5 allele Cre recombinase transgene

Tumor formation upon Pax5 loss in B cells Kaplan Meier survival plot Cobaleda et al. (2007) Nature

Tumors by dedifferentiation to early progenitor cell stage Question: dedifferentiation also under non-oncogenic conditions? Pax5 loss Pax5 = tumor suppressor gene of B-lymphoid lineage tumor with immunoglobulin rearrangements

B cell plasticity in response to Pax5 loss

+ immunoglobulin rearrangements Journey of the mature Pax5-deficient B cells

Pax5 = critical regulator of B cell identity Developmental plasticity of mature B cells

gene deletion gene addition Dedifferentiation versus Transdifferentiation

Conversion of fibroblasts into pluripotent stem cells Ectopic expression of 4 transcription factors Mouse: Okita et al. Nature 448, Wernig et al. Nature 448, Human:Takahashi et al. Cell 131, Yu et al. Science 318,