2011
DOI: 10.1182/blood-2011-03-340554
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Dependency on the polycomb gene Ezh2 distinguishes fetal from adult hematopoietic stem cells

Abstract: Polycomb-group (PcG) proteins are essential regulators of hematopoietic stem cells (HSCs). In contrast to Bmi1, a component of Polycomb repressive complex 1 (PRC1), the role of PRC2 and its components in hematopoiesis remains elusive. Here we show that Ezh2, a core component of PRC2, is essential for fetal, but not adult, HSCs. Ezh2-deficient embryos died of anemia because of insufficient expansion of HSCs/progenitor cells and defective erythropoiesis in fetal liver. Deletion of Ezh2 in adult BM, however, did … Show more

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Cited by 187 publications
(213 citation statements)
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“…Inactivation of Ezh2 can be partially compensated in ES cells, where the inactivation of Ezh2 is associated with milder functional defects than the inactivation of Eed (16). Recently, it has been suggested that in normal hematopoiesis, Ezh1 compensates for inactivation of Ezh2 in adult but not fetal cells (31). In murine MLL-AF9 leukemia, we found a significant number of genes in which H3K27me3 is retained after Ezh2 inactivation.…”
Section: Discussionmentioning
confidence: 63%
See 1 more Smart Citation
“…Inactivation of Ezh2 can be partially compensated in ES cells, where the inactivation of Ezh2 is associated with milder functional defects than the inactivation of Eed (16). Recently, it has been suggested that in normal hematopoiesis, Ezh1 compensates for inactivation of Ezh2 in adult but not fetal cells (31). In murine MLL-AF9 leukemia, we found a significant number of genes in which H3K27me3 is retained after Ezh2 inactivation.…”
Section: Discussionmentioning
confidence: 63%
“…Our data suggest that modulation of polycomb function may be a strategy to therapeutically decrease expression of Myc transcriptional targets, at least in MLL-AF9 leukemia. In this respect it is reassuring that Ezh2 does not appear required for adult normal hematopoietic stem cell function (31). There is little doubt that a cure for MLL-AF9 AML will require combination therapies.…”
Section: Discussionmentioning
confidence: 99%
“…Moreover, previous studies have shown that EZH2 promotes progression, invasion and induces cisplatin resistance in NSCLC [49,50]. As EZH1 is highly homologous to EZH2 and thus shared similar enzyme function with EZH2 [51][52][53], it is likely that EZH1 also contributes to the tumor phenotypes and erlotinib resistance in NSCLC. Thus, it deserves further investigation on how EZH1 mediates erlotinib resistance of NSCLC.…”
Section: Discussionmentioning
confidence: 94%
“…Although EZH2 is required for stem/progenitor cell expansion in developmental hematopoiesis, EZH2 depletion in adult bone marrow is less severe, with no effect on LSK cells, but impaired differentiation of lymphoid cells, and increased myelo-erythroid progenitors, suggesting that EZH2 does regulate at least some stages of myeloid differentiation. 49 Future studies will clarify whether EZH2 specifically regulates C/EBPα function in MA9 cells or in a broader spectrum of cell types.…”
mentioning
confidence: 99%