Gene Expression data human HSCs with 2-LSD1 inhibitors
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA548913 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Human CB HSC enriched fractions were treated with LSD1 inhibitor 2-PCPA and UM171 to identify differntially regulated genes by these compounds.
2019-06-15 | GSE132747 | GEO
Project description:LSD1 is a demethylase of histone modification H3k4me1 and H3K4me2. We have developed novel LSD1 inhibitors (NCD25 and NCD38) and found that they are effective to myelodysplastic syndromes and leukemia cells. To understand what mechanisms are affected by these compounds, we employed gene expression profiling analyses. Gene expression profiling data were obtained from HEL, MDS-L, or CMK11-5 cells treated with DMSO (control), NCD25, or NCD38 and compared each other. Expression of eleven transcriptional factors (GFI1, CEBPA, SPI1, MNDA, TAL1, GATA1, NFE2, RXRA, HOXA9, GATA2, and PBX1) was reconfirmed by q-PCR with the same samples. Gene expression of leukemia cells was measured after 48 hours incubation with or without LSD1 inhibitors. Five independent experiments were performed using 3 cell lines (HEL, MDS-L and CMK11-5) and 2 drugs (NCD38 and NCD25).
2015-04-29 | E-GEOD-68348 | biostudies-arrayexpress
Project description:LSD1 is a demethylase of histone modification H3k4me1 and H3K4me2. We have developed novel LSD1 inhibitors (NCD25 and NCD38) and found that they are effective to myelodysplastic syndromes and leukemia cells. To understand what mechanisms are affected by these compounds, we employed gene expression profiling analyses. Gene expression profiling data were obtained from HEL, MDS-L, or CMK11-5 cells treated with DMSO (control), NCD25, or NCD38 and compared each other. Expression of eleven transcriptional factors (GFI1, CEBPA, SPI1, MNDA, TAL1, GATA1, NFE2, RXRA, HOXA9, GATA2, and PBX1) was reconfirmed by q-PCR with the same samples.
2015-04-29 | GSE68348 | GEO
Project description:We discovered that mice that lack Lsd1 in hematopoietic cells were exhibited increased frequencies of CD150+ CD48- lin- c-Kit+ Sca-1+ LT-HSCs, but completely lacked the lin- c-Kit+ Sca-1- myeloid progenitor compartment. To determine the genes altered by Lsd1-loss, CD150+ CD48- lin- c-Kit+ Sca-1+ LT-HSCs from Lsd1fl/fl and Lsd1fl/fl Mx1Cre mice were FACS-purified to be analyzed by gene expression profiling.
2013-06-25 | GSE40284 | GEO
Project description:The histone de-methylase LSD1 is over-expressed in different haematological tumours, like AML, where it sustains carcinogenesis by promoting the clonogenic potential of leukemic stem cells. Emerging as a promising epigenetic target for the treatment of these tumour types, various LSD1 inhibitors have been developed in the last years, despite their mechanism of action in cancer cells is often not fully clarified. In this study, we characterized a novel mode of action of the inhibitors MC2580 and DDP-38003 and demonstrated that they trigger myeloid differentiation of AML by down-regulating GSE1 protein, a LSD1 interactor on chromatin. By studying the phenotypic effects of GSE1 depletion in NB4 cells, we observed a strong decrease of cell proliferation in vitro, and of tumour growth in vivo. Comparing the transcriptomic changes induced by GSE1 knock-down with those elicited by LSD1 pharmacological inhibition, we found a common set of genes up-regulated and linked with immune response and cytokine-mediated signalling. Mechanistically, we found that several promoters of these genes are bound by both LSD1 and GSE1 at basal state and that GSE1 binding is strongly reduced upon LSD1 inhibition, as a consequence of its reduced expression. By describing for the first time that LSD1-GSE1 interaction on chromatin enforces the silencing of genes linked to myeloid differentiation and by highlighting that this interaction can be overcome by LSD1 inhibitors, our study offers a new perspective on the use of these compounds to trigger differentiation in leukaemia through GSE1 modulation.
2021-12-01 | GSE164559 | GEO
Project description:The histone de-methylase LSD1 is over-expressed in different haematological tumours, like AML, where it sustains carcinogenesis by promoting the clonogenic potential of leukemic stem cells. Emerging as a promising epigenetic target for the treatment of these tumour types, various LSD1 inhibitors have been developed in the last years, despite their mechanism of action in cancer cells is often not fully clarified. In this study, we characterized a novel mode of action of the inhibitors MC2580 and DDP-38003 and demonstrated that they trigger myeloid differentiation of AML by down-regulating GSE1 protein, a LSD1 interactor on chromatin. By studying the phenotypic effects of GSE1 depletion in NB4 cells, we observed a strong decrease of cell proliferation in vitro, and of tumour growth in vivo. Comparing the transcriptomic changes induced by GSE1 knock-down with those elicited by LSD1 pharmacological inhibition, we found a common set of genes up-regulated and linked with immune response and cytokine-mediated signalling. Mechanistically, we found that several promoters of these genes are bound by both LSD1 and GSE1 at basal state and that GSE1 binding is strongly reduced upon LSD1 inhibition, as a consequence of its reduced expression. By describing for the first time that LSD1-GSE1 interaction on chromatin enforces the silencing of genes linked to myeloid differentiation and by highlighting that this interaction can be overcome by LSD1 inhibitors, our study offers a new perspective on the use of these compounds to trigger differentiation in leukaemia through GSE1 modulation.
2021-12-01 | GSE164553 | GEO
Project description:LSD1 inhibitors trigger myeloid differentiation by targeting the LSD1-GSE1 interaction on chromatin
| PRJNA691206 | ENA
Project description:Pharmacological small molecules that target fetal hemoglobin (HbF) repressors serve as potent, cost-effective, and accessible therapeutic strategies to β-globinopathies such as sickle cell disease (SCD). LSD1 inhibition has been shown to induce HbF levels both in vitro and in vivo. However, all potent LSD1 inhibitors in HbF induction in vivo are covalent irreversible compounds, which can cause some adverse effects. In this study, we utilized structure-aided drug design based on the scaffold of a reversible LSD1 inhibitor GSK-690, and developed potent new reversible LSD1 inhibitors that induce robust γ-globin expression in human primary erythroid differentiation culture. Moreover, in a transgenic mouse model of SCD, oral administration of the novel LSD1 inhibitors induces significant elevation of HbF levels and alleviates the disease pathologies resulted from SCD. In addition, combined treatment of an BRD4 degrader, BD-9136 with the LSD1 inhibitors represses the induction of RUNX1 and PU.1, therefore rescues the yield of erythroid cells caused by LSD1 inhibition. Our data indicate that our novel LSD1 inhibitors can effectively induce HbF levels and reduce disease pathologies in SCD mice, and are well-tolerated by oral administration. We anticipate that these new compounds will offer new therapeutic possibilities for treating SCD.
2025-05-15 | GSE275880 | GEO
Project description:Gene expression data for BET inhibitors
| PRJNA713975 | ENA
Project description:Gene expression profile of HSCs and ANGPTL2 treated HSCs Transcriptomes
| PRJNA715219 | ENA