PhD defence C. (Cansu) Koyunlar

Dissertation in short:

Hematopoietic stem cells (HSCs) are the sole precursors of the hematopoietic system that can self-renew and differentiate into all mature blood cell types. The transcription factor (TF) GATA2 is highly expressed in HSCs and regulates the HSC generation during embryonic development and HSC function throughout adulthood. In patients, heterozygous GATA2 mutations cause GATA2 haploinsufficiency syndromes that present with a broad spectrum of phenotypes such as B-cell-, monocyte-, NK cell- and dendritic cell deficiencies, primary lymphedema, and more than 80% risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Although GATA2 mutations evidently lead to hematopoietic defects in patients, the mechanisms underlying GATA2 haploinsufficiency phenotypes are relatively unknown. In this thesis, we examine the multifaceted role of GATA2 throughout the formation and function of HSCs, the building blocks of the hematopoietic system, in both Gata2-mutant zebrafish and mouse models.