biostudies-literatureStaehle HFDeutsche Forschungsgemeinschaft (German Research Foundation)619https://www.ebi.ac.uk/biostudies/studies/S-EPMC12354751biostudies-literatureUnknown16(1)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 functioCell death & diseaseLysine-specific demethylase 1 regulates hematopoietic stem cell expansion and myeloid cell differentiation.PMC12354751RI 1283/15-1/2MA 7792/1-1/2PE 3217/4-1Pa 611/9-1/2Ju 31041/1-1Pa 611/11-1JU 3104/2-1Br 3535/2-1/2Pa 611/5-3Muller JMImbusch CDStaehle AMAttia AZell FPozdnyakova OMallm JPPahl HLSchule RMetzger EStaehle HFEble PRippe KFeuerbach LMuller ABrors BJutzi JSKoellerer CSchulze JPerner FfalseLysine-specific demethylase 1 regulates hematopoietic stem cell expansion and myeloid cell differentiation.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 functio2025-01-01T00:00:00Z2025 Aug2026-07-15T14:11:33.705Z2026-07-06T03:08:40.917ZS-EPMC123547514081357410.1038/s41419-025-07951-z