University of Dundee

"STAT5A and STAT5B – more than identical twins in hematopoiesisi and leukemogenesis”

Event Date: 
Wednesday, February 10, 2021 - 13:00 to 14:00
Event Location: 
Zoom
Host: 
Dr. Ignacio Moraga Gonzalez
Event Speaker: 
Prof. Veronika Sexl
Institution: 
University of Vienna
Event Type: 
Seminar
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Abstract 
Sebastian Kollmann, Barbara Maurer & Veronika Sexl
 
1 Institute of Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria
 
Signal transducer and activator of transcription (STAT) 5 is encoded by two adjacent genes, STAT5A and STAT5B, which act as transcription factors and share more than 96% protein identity. Conditional deletion of Stat5 leads to a depletion of the long-term hematopoietic stem cell (HSC) pool underlining the importance of STAT5 in HSCs. The fact that gain-of-function mutations in hematopoietic cancers are predominantly found in STAT5B, but not STAT5A, indicates distinct functions of the two proteins within the hematopoietic system. In line, recent studies using STAT5A and STAT5B leukemic mouse models point at specific functions for each isoform.
 
We used murine models either deficient for Stat5a or Stat5b to investigate the consequences on HSC self-renewal capacity. Our data propose a key role for STAT5B in maintaining stem cell self-renewal, which is not shared by its isoform STAT5A. Transcriptional profiling supports these findings and uncover gene sets associated with STAT5B specific HSC quiescence. To gain further insights into how STAT5A and STAT5B effect leukemic stem cell (LSC)-driven diseases, we generated LSC model systems either lacking Stat5a or Stat5b to mimic typical stem cell diseases. The absence of Stat5b significantly impaired leukemic transformation and proliferation.
 
These findings pinpoint at novel, yet unidentified roles of STAT5A and STAT5B within the HSC and LSC pool and help understand why mutations in hematopoietic cancers are predominantly found in STAT5B.
 

This work is funded by the Austrian Science Fund SFB F6107.