RNAseq of control and GFI1-expressing A549
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE165307 | GEO | 2022/09/14
REPOSITORIES: GEO
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Project description:To investigate the genes regulated by the transcription factor GFI1 in lung cancer cells, we overexpressed GFI1-Flag in A549 cells and performed ChIP-Seq with anti-Flag affinity gel.
2022-09-14 | GSE164984 | GEO
Project description:The zinc finger transcription factor growth-factor-independent-1 (Gfi1) has been involved in various cellular differentiation processes. Gfi1 acts as a transcriptional repressor and splicing control factor upon binding to cognate binding sites in regulatory elements of its target genes. Here, we report that Gfi1-deficient mice develop autoimmunity. Gfi1-deficient peripheral B-cells show a hyperproliferative phenotype, leading to expansion of plasma cells, increased levels of nuclear autoantibodies, and immunoglobulin deposition in brain and kidneys. Dysregulation of multiple transcription factors and cell-cycle control elements may contribute to B-cell dependent autoimmunity. Gfi1 thus emerges as a novel master-regulator restricting autoimmunity. Experiment Overall Design: Splenic B220+CD19+ CD138- B cells of 4 week old Gfi1+/+ and Gfi1-/- mice were isolated and RNA was extracted from one sample per group and microarray analysis was performed.
2008-10-25 | E-GEOD-12545 | biostudies-arrayexpress
Project description:Growth factor independent 1 (Gfi1) is a transcriptional repressor originally identified as a common integration site in Moloney-murine-leukemia-virus-induced T-cell leukemia. Gfi1-/- mice display increased apoptosis of developing thymocytes and T lymphopenia; however, there are contradictory reports of the absolute number of Gfi1-/- early T lineage progenitors. We used floxed alleles of Gfi1 crossed to various T-cell-specific Cre transgenes to map the requirements for Gfi1 during lymphoid priming and development. We show that Gfi1 is necessary for the proper formation and function of both lymphoid-primed multipotent progenitors and early T lineage progenitors. These defects correlate with a global inability of Gfi1-/- progenitors to enforce the activation of lymphoid genes including IL7R, Rag1, Flt3 and Notch1. Forced expression of intracellular Notch1 fails to rescue the Gfi1-/- defective lymphoid gene signature or Gfi1-/- T cell development. Instead, activation of Notch1 in Gfi1-/- cells results in a potent synthetic lethal phenotype that is most dramatic in immature thymocytes, but absent in mature peripheral T cells where developmental transcriptional programs are silent. Moreover, we find that the requirement for Gfi1-transcriptional integration of Notch-driven lymphoid transcriptional programs is cell autonomous. Our data indicate that Gfi1 is required at multiple independent stages of lymphoid development. In hematopoietic progenitors Gfi1 is necessary to integrate Notch1 signaling, mediate lymphoid priming, the formation of early T lineage progenitors and subsequent T lineage commitment. Lineage negative cells were purified by magnetic beads from RosaCreERT2 Gfi1 ex4-5 floxed mice and an activated Notch1 signal was introduced using a GFP+ retroviral vector. GFP+ progenitors were FACS-sorted and cultured in semi-solid media for one week to allow sufficient time to to instruct lymphoid differentiation, then replated in 1uM 4-OHT or EtOH control. After an additional 7 days, CFU were disrupted and RNA was isolated for global gene expression using microarrays.
2014-10-01 | E-GEOD-41162 | biostudies-arrayexpress
Project description:Growth factor independent 1 (Gfi1) is a transcriptional repressor originally identified as a common integration site in Moloney-murine-leukemia-virus-induced T-cell leukemia. Gfi1-/- mice display increased apoptosis of developing thymocytes and T lymphopenia; however, there are contradictory reports of the absolute number of Gfi1-/- early T lineage progenitors. We used floxed alleles of Gfi1 crossed to various T-cell-specific Cre transgenes to map the requirements for Gfi1 during lymphoid priming and development. We show that Gfi1 is necessary for the proper formation and function of both lymphoid-primed multipotent progenitors and early T lineage progenitors. These defects correlate with a global inability of Gfi1-/- progenitors to enforce the activation of lymphoid genes including IL7R, Rag1, Flt3 and Notch1. Forced expression of intracellular Notch1 fails to rescue the Gfi1-/- defective lymphoid gene signature or Gfi1-/- T cell development. Instead, activation of Notch1 in Gfi1-/- cells results in a potent synthetic lethal phenotype that is most dramatic in immature thymocytes, but absent in mature peripheral T cells where developmental transcriptional programs are silent. Moreover, we find that the requirement for Gfi1-transcriptional integration of Notch-driven lymphoid transcriptional programs is cell autonomous. Our data indicate that Gfi1 is required at multiple independent stages of lymphoid development. In hematopoietic progenitors Gfi1 is necessary to integrate Notch1 signaling, mediate lymphoid priming, the formation of early T lineage progenitors and subsequent T lineage commitment.
2014-10-01 | GSE41162 | GEO
Project description:To study the effect of transcription factor GFI1 on lung cancer cells, we knockouted GFI1 in H1155 cells by CRISPR/Cas9 and performed RNA-seq.
2022-09-14 | GSE165308 | GEO
Project description:GFI1 is a transcriptional repressor protein that plays an essential role in HSCs development, lymphoid and myeloid differentiation and Acute Myeloid Leukaemic (AML) pathogenesis. Low expression levels of GFI1 is associated with a poor prognosis in AML development. In addition, a single nucleotide polymorphism (SNP) variant of GFI1 results in the generation of GFI1 protein with asparagine (N) instead of serine (S) at the 36th amino acid position, known as GFI136N. Expression of the GFI1-36N allele leads as well to poor prognosis and promotes AML development. In this study, we demonstrated with the help of RNAseq transcriptomic analysis that the presence of GFI1-36N is associated with increased frequency of chromosomal aberrations and mutational burden in murine and human AML cells. In particular, GFI1-36N modulates DNA repair pathways, O6-methylguanine-DNA-methyltransferase (MGMT)-mediated repair and homologous recombination repair (HR). Mechanistically, GFI1-36N exhibits impaired binding to Ndrg1 promoter element compared to GFI1-36S (wild type), causing decreased NDRG1 levels, consequently leading to suppression of MGMT expression, imprinted at the transcriptome and proteome, thus leaving the AML cells vulnerable to DNA damaging agents. Furthermore, we showed that a low expression level of GFI1 in leukemic cells is associated with high OXPHOS and enhanced glutamine metabolism. However, we hypothesise that the observed metabolic phenotype is mediated through FOXO1 protein. RNAseq transcriptomic analysis revealed higher Foxo1 mRNA expression levels with lower GFI1 expression, providing the first hint of Foxo1 as a potential target gene of GFI1 protein. The mRNA and protein levels of high Foxo1 with reduced GFI1 expression was confirmed by RT-PCR and western blot, respectively. In addition, CHIPseq and ATACseq analysis further proved that Foxo1 is a potential target gene of GFI1. In summary, we show that GFI1 plays a role during DNA repair and metabolism and thus provides critical insights into a novel therapeutic option for AML patients carrying the GFI1-36N variant or having a low expression level of GFI1.
2023-12-01 | GSE195955 | GEO
Project description:GFI1 is a transcriptional repressor that plays an essential role in HSCs development, lymphoid and myeloid differentiation and Acute Myeloid Leukemia (AML) pathogenesis. Low expression of Gfi1 leads to poor prognosis in AML patients and is associated with less overall survival in murine AML models. In the current study, we show that mice with a low level or loss of GFI1 expression resulted in significantly fewer HSCs compared to normal GFI1 expression. We also show that, in a competitive transplantation setup involving cells expressing low and normal GFI1 levels, HSCs with a low level of GFI1 expression reconstituted the bone marrow (BM) including the HSCs, progenitors and differentiated cells. In contrast, HSCs with the complete loss of GFI1 failed to regenerate BM in competition with cells expressing normal GFI1 levels. To further investigate the molecular changes, we performed RNAseq analysis in HSCs derived from wildtype (GFI1-KI), low-level (GFI1-KD), loss (Gfi1-KO) and Gfi1 mutant (GFI1-36N) mice. In the pathway analysis, we observed a significant upregulation of cell-cycle-related pathways in HSCs derived from mice expressing low-level and mutant variant (36N) of GFI1., Strikingly, these pathways are significantly downregulated in the HSCs of GFI1-KO mice.
2023-05-12 | GSE225653 | GEO
Project description:In order to indentify the transcriptional differences between GFI1 KD and GFI1 KO mice that may account for differences in occurence of AML between these mice, we performed exresiion profiling by RNA-Seq on healthy young and old mice mice from both genotypes. In the case of GFI1 KD, the older mice had developped AML whereas KO mice of comparable ages did not.
2018-06-01 | GSE102957 | GEO
Project description:Abarrent transcriptional regulation is one of hallmarks of leukemia. GFI1 is a transcriptional regulator with context-dependent roles in hematopoiesis and leukemogenesis. Reduced or loss of GFI1 expression has been reported in myeloid malignancies, while high GFI1 expression has been observed in AML1-ETO-positive acute myeloid leukemia (AML) and acute lymphoid leukemia, but without clear roles defined for GFI1 in APL pathogenesis. We here performed ChIP-seq analysis using antibodies against GFI1 and identified genome-wide binding site of GFI1 in NB4 cells.
2020-08-26 | GSE154269 | GEO
Project description:Fresh peripheral blood mononuclear cells of four human donors were cultured together with either lung adenocarcinoma A549 cancer cells or A549-expressing H1N1 Sialidase cancer cells. These treatments induced the differentiation of donor cells into immunosuppressive MDSC-like cells, which were further subjected to bulk RNA sequencing. Computational analysis of RNA-Seq profiles of these cells was applied to understand the differences in their suppressive capacities.
| EGAS00001007618 | EGA