Expression data comparing EBF1 versus Pax5 induced genes
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE46004 | GEO | 2013/04/12
SECONDARY ACCESSION(S): PRJNA196864
REPOSITORIES: GEO
Similar Datasets
Project description:We used microarrays to establish whether EBF1 and Pax5 repress similar or unique genes. We found that EBF1 uniquely represses the expression of the T-lineage transcription factor Gata3. Ebf1-/- pre-pro-B cells were transduced with either control MigR1, MigY-EBF1 or MigR-Pax5 viruses. 24 hours later, RNA was isolated and processed for Affymetrix microarray analysis. Cells expressing EBF1, Pax5, or neither were sorted and processed. Scale represents log2 value of normalized signal level.
2013-04-12 | E-GEOD-46004 | biostudies-arrayexpress
Project description:STAT5 is critical for differentiation, proliferation and survival of progenitor B cells suggesting a possible role in Acute Lymphoblastic Leukemia (ALL). Herein, we show increased expression of activated STAT5 in ALL patients, which correlates with treatment outcome. Mutations in Ebf1 and Pax5, genes critical for B cell development have also been identified in human ALL. To determine whether mutations in Ebf1 or Pax5 synergize with STAT5 activation to induce ALL we crossed mice expressing a constitutively active form of STAT5 (Stat5b-CA) with mice heterozygous for Ebf1 or Pax5. Haploinsufficiency of either Pax5 or Ebf1 synergized with Stat5b-CA to rapidly induce ALL in 100% of the mice. The leukemic cells displayed reduced expression of both Pax5 and Ebf1 but this had little affect on most EBF1 or PAX5 target genes. However, a subset of these genes was deregulated and included a large percentage of potential tumor suppressor genes and oncogenes. Further, most of these genes appear to be jointly regulated by both EBF1 and PAX5. Our findings suggest a model whereby small perturbations in a self-reinforcing network of transcription factors critical for B cell development, specifically PAX5 and EBF1, cooperate with STAT5 activation to initiate ALL. Gene expression profiling was performed on cells isolated from lymph nodes of Stat5b-CA x Ebf1+/- and Stat5b-CA x Rag2-/- leukemic mice and pre B cells sorted from bone marrow of C57BL/6 mice and Stat5b-CA transgenic mice. 17 Samples.
2011-05-09 | E-GEOD-25645 | biostudies-arrayexpress
Project description:STAT5 is critical for differentiation, proliferation and survival of progenitor B cells suggesting a possible role in Acute Lymphoblastic Leukemia (ALL). Herein, we show increased expression of activated STAT5 in ALL patients, which correlates with treatment outcome. Mutations in Ebf1 and Pax5, genes critical for B cell development have also been identified in human ALL. To determine whether mutations in Ebf1 or Pax5 synergize with STAT5 activation to induce ALL we crossed mice expressing a constitutively active form of STAT5 (Stat5b-CA) with mice heterozygous for Ebf1 or Pax5. Haploinsufficiency of either Pax5 or Ebf1 synergized with Stat5b-CA to rapidly induce ALL in 100% of the mice. The leukemic cells displayed reduced expression of both Pax5 and Ebf1 but this had little affect on most EBF1 or PAX5 target genes. However, a subset of these genes was deregulated and included a large percentage of potential tumor suppressor genes and oncogenes. Further, most of these genes appear to be jointly regulated by both EBF1 and PAX5. Our findings suggest a model whereby small perturbations in a self-reinforcing network of transcription factors critical for B cell development, specifically PAX5 and EBF1, cooperate with STAT5 activation to initiate ALL.
2011-05-09 | GSE25645 | GEO
Project description:In order to investigate how transcription factor dose impacts B-lymphocyte development, we generated mice carrying transheterozygous mutations in the Pax5 and Ebf1 genes. While combined reduction of Pax5 and Ebf1 dose had minimal impact on the development of the earliest CD19+ progenitors, these cells displayed an increased T-cell potential in vivo and in vitro. Alteration in lineage fate depended on a Notch1 mediated conversion process while no signs of de-differentiation could be detected. The differences in functional response to Notch signaling in Wt and Pax5+/-Ebf1+/- pro-B cells was reflected in the transcriptional response because even though cells of both genotypes responded by the generation of intracellular Notch1 and activation of a set of target genes, only the Pax5+/-Ebf1+/- pro-B cells down-regulated genes central for the preservation of stable B-cell identity. This report stresses the importance of transcription factor dose in lymphocyte development and suggests that Pax5 and Ebf1 collaborate to modulate the transcriptional response to Notch signaling after the generation of activated intracellular Notch1. This provides an insight to how transcription factors like Ebf1 and Pax5 preserve cellular identity during differentiation. EBF-1 ChIP-seq: Cultivated CD43+IgM- cells (ProB) cells from Wt, EBF-1 +/-, PAX-5 +/- and EBF-1 +/- PAX-5 +/- (TH) were assessed for EBF-1 binding by ChIP-seq. Replicate Ebf1 ChIP-seq runs on each genotype (Wt, TH, Ebf1+/- and Pax5+/-) and corresponding inputs were pooled into one dataset and analyzed as one combined sample per genotype. RNA-seq no treatment: Briefly, ProB-cells from C57BL/6J Ebf1+/-Pax5+/- (n=4), WT (n=4), Ebf1+/- (n=2) and Pax5+/- (n=2) were sorted and RNA extracted with Qiagen RNeasy Micro Kit. RNA was sent to UCLA Microarray Core for library preparation and were subsequently for 50 cycles of HiSeq 2000 SBS sequencing generating 20-30 million reads/sample. Data analysis was performed with Arraystar® (DNASTAR)). RNA-seq 1 day on OP9DL1 and OP9: In short, in vitro expanded ProB-cells from C57BL/6J Ebf1+/-Pax5+/- (n=4) and WT (n=4) were exposed either on OP9 or OP9-DL1 stromal cells for 24 hours and RNA extracted with Qiagen RNeasy Micro Kit. Due to low reads, two Wt and Ebf1+/-Pax5+/- were sequenced twice. Libraries were constructed using Nugen's Ovation Ultralow Library systems and were subsequently for 50 cycles of NextSeq500 sequencing generating 20-30 million reads/sample. Data analysis was performed with Arraystar® (DNASTAR)).
2015-05-27 | E-GEOD-69227 | biostudies-arrayexpress
Project description:ATACSeq, EBF1 ChIPSeq and Pax5 ChIPSeq of dHet B-ALL, dHet proB and wt proB cells.
2020-10-19 | GSE158671 | GEO
Project description:In order to investigate how transcription factor dose impacts B-lymphocyte development, we generated mice carrying transheterozygous mutations in the Pax5 and Ebf1 genes. While combined reduction of Pax5 and Ebf1 dose had minimal impact on the development of the earliest CD19+ progenitors, these cells displayed an increased T-cell potential in vivo and in vitro. Alteration in lineage fate depended on a Notch1 mediated conversion process while no signs of de-differentiation could be detected. The differences in functional response to Notch signaling in Wt and Pax5+/-Ebf1+/- pro-B cells was reflected in the transcriptional response because even though cells of both genotypes responded by the generation of intracellular Notch1 and activation of a set of target genes, only the Pax5+/-Ebf1+/- pro-B cells down-regulated genes central for the preservation of stable B-cell identity. This report stresses the importance of transcription factor dose in lymphocyte development and suggests that Pax5 and Ebf1 collaborate to modulate the transcriptional response to Notch signaling after the generation of activated intracellular Notch1. This provides an insight to how transcription factors like Ebf1 and Pax5 preserve cellular identity during differentiation.
2015-05-27 | GSE69227 | GEO
Project description:Here, we report that EBF1 and Pax5 collaborate in a dose-dependent manner to regulate the IL-7-STAT5 signaling pathway and one-carbon metabolism, whereby we found both diminished and enhanced binding of EBF1 and Pax5 to target genes in compound heterozygous mutant mice. Moreover, single-cell RNA sequencing analysis identified a small subset of wild-type pro-B cells on the trajectory to pre-B cells that share gene expression signatures with leukemic Ebf1+/−Pax5+/− pro-B cells. Thus, a normal expression level of EBF1 and Pax5 is required for safeguarding a potentially vulnerable pro-Bcell subset from a transformation to B-ALL.
2020-10-19 | GSE158827 | GEO
Project description:Lineage restricted transcription factors are frequently found mutated in B-lymphoid leukemia, suggesting a close link between normal and malignant B-cell development. One of these transcription factors is EBF1, a protein of critical importance for specification but also survival of B-lymphoid progenitors. We here report that impaired EBF1 function in mouse B-cell progenitors results in reduced expression of Myc. Ectopic expression of MYC rescued B-cell expansion in the absence of EBF1 both in vivo and in vitro. Using chromosome conformation analysis in combination with ATAC, ChIP-seq and reporter gene assays, identified six EBF responsive enhancer elements that could be annotated to the Myc gene. Crispr-Cas9 mediated targeting of EBF1 binding sites identified one element of importance for Myc expression and pro-B cell expansion providing evidence for that Myc is a direct target for EBF1. Furthermore, ChIP-seq analysis suggested that several regulatory elements in the Myc gene were targeted by PAX5. However, ectopic expression of PAX5 in EBF1 deficient cells was found to induce a cell cycle block and reduce Myc expression suggesting that EBF1 and PAX5 act in an opposing manner at this shared target gene. This hypothesis was further substantiated by the finding that Pax5 inactivation reduced the need for EBF1 in pro-B cell expansion. The binding of EBF1 and PAX5 to regulatory elements in the human MYC gene in a B-ALL cell line indicate that this regulatory loop may be of relevance for our understanding of both normal and malignant B-cell development.
2021-03-05 | GSE159957 | GEO
Project description:EBF1 and PAX5 are two transcription factors targeted in human B-ALL. Their importance for normal B-cell differentiation has led to the suggestion that impaired function of these proteins contributes to the developmental block observed in B-lineage leukemia. However, increased understanding of the function of these proteins has suggested more complex roles in malignant transformation. We here report that the loss of EBF1 function in B-cell progenitors results in reduced expression of c-MYC. Ectopic expression of c-MYC rescues B-cell expansion in the absence of EBF1 both in vivo and in vitro and ChIP-seq analysis identifies multiple binding sites for EBF1 in putative regulatory elements of the mouse c-Myc gene. On the contrary, expression of PAX5 in EBF1 deficient cells resulted in down regulation of c-Myc and inhibition of cell expansion. Since both EBF1 and PAX5 bind multiple regulatory elements in the c-Myc gene, these data suggest that EBF1 and PAX5 have opposing functions with regard to regulation of c-Myc expression. This suggests the existence of a lineage restricted regulatory loop controlling the expansion of B-lineage progenitors. The binding of EBF1 and PAX5 to multiple regulatory elements in the human c-MYC gene indicate that this regulatory loop may be of relevance for our understanding of leukemia formation.
2019-11-30 | GSE136238 | GEO
Project description:To profile gene expression changes in Ebf1+/-Pax5+/- (dHet) leukemic mice, we performed RNASeq analysis in dHet B-ALL, dHet proB and wt proB cells.
2020-10-19 | GSE158661 | GEO