2013
DOI: 10.7554/elife.00633
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Histone demethylase Lsd1 represses hematopoietic stem and progenitor cell signatures during blood cell maturation

Abstract: Here, we describe that lysine-specific demethylase 1 (Lsd1/KDM1a), which demethylates histone H3 on Lys4 or Lys9 (H3K4/K9), is an indispensible epigenetic governor of hematopoietic differentiation. Integrative genomic analysis, combining global occupancy of Lsd1, genome-wide analysis of its substrates H3K4 monomethylation and dimethylation, and gene expression profiling, reveals that Lsd1 represses hematopoietic stem and progenitor cell (HSPC) gene expression programs during hematopoietic differentiation. We f… Show more

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Cited by 236 publications
(287 citation statements)
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“…The importance of LSD1 in hematopoiesis has previously been shown using cultured cells (44)(45)(46), knockdown mice (47), and conditional KO mice (48). In addition, the contribution of LSD1 in leukemogenesis has been demonstrated, and the use of LSD1 inhibitors is being investigated as a new therapeutic strategy (49,50).…”
Section: Discussionmentioning
confidence: 98%
See 1 more Smart Citation
“…The importance of LSD1 in hematopoiesis has previously been shown using cultured cells (44)(45)(46), knockdown mice (47), and conditional KO mice (48). In addition, the contribution of LSD1 in leukemogenesis has been demonstrated, and the use of LSD1 inhibitors is being investigated as a new therapeutic strategy (49,50).…”
Section: Discussionmentioning
confidence: 98%
“…In addition, the contribution of LSD1 in leukemogenesis has been demonstrated, and the use of LSD1 inhibitors is being investigated as a new therapeutic strategy (49,50). The roles of LSD1 in hematopoiesis are various, and include the differentiation switch between erythropoiesis and myelopoiesis (44), the terminal differentiation of some hematopoietic lineages (47,48), maintenance of the undifferentiated state of plasma cells (46), globin switching (51)(52)(53), and the self-renewal of hematopoietic stem cells (48). Here, we unveiled new roles of LSD1, as a down-regulator of the endothelial characteristics and promoter of the hematopoietic commitment in hemangioblasts.…”
Section: Discussionmentioning
confidence: 99%
“…On the other hand, LSD1 was shown to be essential for the self-renewal and proper differentiation of HSCs in conditional LSD1 knockout mice. 18 Furthermore, it is of note that LSD1 expression is elevated in neuroblastoma and bladder cancer 19,20 and is correlated with a poor prognosis in hormonedependent prostate and breast cancers. 21 From these observations, we hypothesized that the expression levels and function of LSD1 are tightly regulated in HSPCs and their deregulation underlies the development of hematologic malignancies.…”
Section: Introductionmentioning
confidence: 99%
“…In a conditional gene knockdown model, LSD1 reduction was found to expand BM progenitor numbers by enhancing their proliferative behavior (20). Additionally, knockout of LSD1 resulted in derepression of stem and progenitor cell gene signatures along with impaired granulocytic and erythroid maturation (21). In the current study, we aim to identify whether LSD1 also acts as an enzymatic partner for SALL4 and how they may function together and coordinately regulate BM progenitor cell proliferation.…”
mentioning
confidence: 96%