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Transkriptionelle Kontrolle der B-Zellplastizität
und Onkogenese durch Pax5
Meinrad Busslinger
Institut für Molekulare Pathologie, Wien
Transkriptionsfaktoren kontrollieren die Genexpression
Pax5
Pax5 definiert die Identität der B-Zelle
B-Zelldifferenzierung
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
tumor
with
immunoglobulin
rearrangements
Pax5 loss
Pax5 = tumor suppressor gene of B-lymphoid lineage
Question: dedifferentiation also under non-oncogenic conditions?
B cell plasticity in response to Pax5 loss
Journey of the mature Pax5-deficient B cells
+
immunoglobulin
rearrangements
Developmental plasticity of mature B cells
Pax5 = critical regulator of B cell identity
Dedifferentiation versus Transdifferentiation
gene deletion
gene addition
Conversion of fibroblasts into pluripotent stem cells
Ectopic expression of
4 transcription factors
Mouse:
Okita et al. Nature 448, 313-317
Wernig et al. Nature 448, 318-324
Human:
Takahashi et al. Cell 131, 861-872
Yu et al. Science 318, 1917-1920