%0 Journal Article
%A Staehle, Hans Felix
%A Koellerer, Christoph
%A Staehle, Anne Marie
%A Schulze, Jana
%A Eble, Philipp
%A Müller, Anja
%A Zell, Franziska
%A Müller, Judith M
%A Perner, Florian
%A Attia, Aya
%A Mallm, Jan-Philipp
%A Pozdnyakova, Olga
%A Rippe, Karsten
%A Brors, Benedikt
%A Feuerbach, Lars
%A Imbusch, Charles D
%A Metzger, Eric
%A Schüle, Roland
%A Pahl, Heike L
%A Jutzi, Jonas S
%T Lysine-specific demethylase 1 regulates hematopoietic stem cell expansion and myeloid cell differentiation.
%J Cell death & disease
%V 16
%N 1
%@ 2041-4889
%C London [u.a.]
%I Nature Publishing Group
%M DKFZ-2025-01711
%P 619
%D 2025
%X The lysine-specific demethylase 1 (LSD1) regulates hematopoietic stem cell differentiation and has been identified as a therapeutic target in hematological disorders. LSD1 demethylates mono and dimethylated histones 3 at lysine 4 and 9. In addition, it acts as a scaffold for the formation of chromatin-modifying complexes that regulates the transcription of myeloid-lineage-specific genes in complex with GFI1, a transcriptional repressor. While both enzymatic and non-enzymatic functions of LSD1 have been well defined, the relative importance of these two functions in hematopoiesis remains incompletely understood. Here, we investigated the contribution of enzymatic and non-enzymatic functions of LSD1 to myelopoiesis. We show that myeloid differentiation is independent of the enzymatic functions of LSD1 but requires the non-enzymatic, scaffolding function, which directs GFI1 binding to target sequences. In the absence of the LSD1 protein, GFI1 DNA binding is diminished, and myeloid cell differentiation arrests at an immature, myelomonocytic-like cell stage, which overexpresses Prtn3. We provide functional data implicating Prtn3 as an effector of the stem cell expansion and myeloid maturation block caused by the loss of LSD1.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40813574
%2 pmc:PMC12354751
%R 10.1038/s41419-025-07951-z
%U https://inrepo02.dkfz.de/record/303647