Transcription factor EBF1 non-cell autonomously regulates cardiac growth and differentiation
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ABSTRACT:
PROVIDER: PRJNA1016462 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26055414_1.fastq.gz | Fastqsanger.gz | |||
| SRR26055414_2.fastq.gz | Fastqsanger.gz | |||
| SRR26055415_1.fastq.gz | Fastqsanger.gz | |||
| SRR26055415_2.fastq.gz | Fastqsanger.gz | |||
| SRR26055416_1.fastq.gz | Fastqsanger.gz |
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Project description:Reciprocal interactions between non-myocytes and cardiomyocytes are implicated in the control of cardiac growth and differentiation. Here, we report the identification of early B-cell factor 1 (Ebf1) as a transcription factor highly enriched in non-myocytes that potently regulates heart development. Postnatal Ebf1 deficient hearts are characterized by marked myocardial hypercellularity and reduced cardiomyocyte size, as well as ventricular conduction system hypoplasia and conduction system disease. Growth abnormalities in Ebf1 knockout hearts are observed as early as embryonic day 13.5, with dysregulated cell cycling, myocardial hyperplasia, and immature trabecular morphology. Transcriptional profiling of Ebf1-deficient non-myocytes isolated from embryonic hearts demonstrates dysregulation of Polycomb repressive complex 2 (PRC2) targets, while ATAC-Seq reveals differences in chromatin accessibility near many of these same genes. Gene set enrichment analysis of differentially expressed genes in cardiomyocytes isolated from E13.5 hearts of wildtype and Ebf1 deficientmice reveals significant enrichment of MYC targets, and consistent with this finding, we observe increased abundance of MYC in mutant hearts. Mechanistically, we show that EBF1-deficient non-myocytes, but not wildtype non-myocytes, are sufficient to induce excessive accumulation of nuclear-localized MYC protein in co-cultured wildtype cardiomyocytes. Finally, we demonstrate that BMP signaling induces Ebf1 expression in embryonic heart cultures and controls a gene program enriched in EBF1 targets. Taken together, these results reveal a novel non-cell autonomous pathway controlling cardiac growth and development.
2023-10-12 | GSE243167 | GEO
Project description:Reciprocal interactions between non-myocytes and cardiomyocytes regulate cardiac growth and differentiation. Here, we report that the transcription factor Ebf1 is highly expressed in non-myocytes and potently regulates heart development. Ebf1-deficient hearts display myocardial hypercellularity and reduced cardiomyocyte size, ventricular conduction system hypoplasia, and conduction system disease. Growth abnormalities in Ebf1 knockout hearts are observed as early as embryonic day 13.5. Transcriptional profiling of Ebf1-deficient embryonic cardiac non-myocytes demonstrates dysregulation of Polycomb repressive complex 2 targets, and ATAC-Seq reveals altered chromatin accessibility near many of these same genes. Gene set enrichment analysis of differentially expressed genes in cardiomyocytes isolated from E13.5 hearts of wild-type and mutant mice reveals significant enrichment of MYC targets and, consistent with this finding, we observe increased abundance of MYC in mutant hearts. EBF1-deficient non-myocytes, but not wild-type non-myocytes, are sufficient to induce excessive accumulation of MYC in co-cultured wild-type cardiomyocytes. Finally, we demonstrate that BMP signaling induces Ebf1 expression in embryonic heart cultures and controls a gene program enriched in EBF1 targets. These data reveal a previously unreported non-cell-autonomous pathway controlling cardiac growth and differentiation.
| S-EPMC10652039 | biostudies-literature
Project description:Transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into differentiation stage-specific functions of Ebf1, we conditionally inactivated Ebf1. We found that Ebf1 is required for proliferation, survival and signaling of pro-B cells and peripheral B cell subsets. The proliferation defect of Ebf1-deficient pro-B cells, including the impaired expression of IL-7Ra and several cell cycle regulators, is overcome by transformation with v-Abl. The survival defect of transformed Ebf1fl/fl pro-B cells can be rescued by the forced expression of the Ebf1 targets c-Myb or Bcl-xL. In mature B cells, Ebf1 deficiency interferes with the BAFF-R and BCR-dependent Akt signaling pathways, as well as with germinal center formation and class switch recombination. Genome-wide analyses of Ebf1 binding and Ebf1-mediated gene expression in mature B cells and comparison with reported data sets in pro-B cells provide insight into the basis for lineage- and stage-specific functions of Ebf1. EBF1 binding in splenic B cells in mice
2012-04-02 | E-GEOD-35910 | biostudies-arrayexpress
Project description:Transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into differentiation stage-specific functions of Ebf1, we conditionally inactivated Ebf1. We found that Ebf1 is required for proliferation, survival and signaling of pro-B cells and peripheral B cell subsets. The proliferation defect of Ebf1-deficient pro-B cells, including the impaired expression of IL-7Ra and several cell cycle regulators, is overcome by transformation with v-Abl. The survival defect of transformed Ebf1fl/fl pro-B cells can be rescued by the forced expression of the Ebf1 targets c-Myb or Bcl-xL. In mature B cells, Ebf1 deficiency interferes with the BAFF-R and BCR-dependent Akt signaling pathways, as well as with germinal center formation and class switch recombination. Genome-wide analyses of Ebf1 binding and Ebf1-mediated gene expression in mature B cells and comparison with reported data sets in pro-B cells provide insight into the basis for lineage- and stage-specific functions of Ebf1.
2012-04-03 | GSE35910 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE35910: Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferative expansion and survival of B cells [EBF1] GSE35914: Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferative expansion and survival of B cells [H3K4me2 and H3K4me3] Refer to individual Series See related Series GSE36061.
2012-04-02 | E-GEOD-35915 | biostudies-arrayexpress
Project description:Transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into differentiation stage-specific functions of Ebf1, we conditionally inactivated Ebf1. We found that Ebf1 is required for proliferation, survival and signaling of pro-B cells and peripheral B cell subsets. The proliferation defect of Ebf1-deficient pro-B cells, including the impaired expression of IL-7Ra and several cell cycle regulators, is overcome by transformation with v-Abl. The survival defect of transformed Ebf1fl/fl pro-B cells can be rescued by the forced expression of the Ebf1 targets c-Myb or Bcl-xL. In mature B cells, Ebf1 deficiency interferes with the BAFF-R and BCR-dependent Akt signaling pathways, as well as with germinal center formation and class switch recombination. Genome-wide analyses of Ebf1 binding and Ebf1-mediated gene expression in mature B cells and comparison with reported data sets in pro-B cells provide insight into the basis for lineage- and stage-specific functions of Ebf1. Localistaion of histone modification (H3K4me2 and H3K4me3) in splenic B cells in mice by ChIP-seq
2012-04-02 | E-GEOD-35914 | biostudies-arrayexpress
Project description:Transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into differentiation stage-specific functions of Ebf1, we conditionally inactivated Ebf1. We found that Ebf1 is required for proliferation, survival and signaling of pro-B cells and peripheral B cell subsets. The proliferation defect of Ebf1-deficient pro-B cells, including the impaired expression of IL-7Ra and several cell cycle regulators, is overcome by transformation with v-Abl. The survival defect of transformed Ebf1fl/fl pro-B cells can be rescued by the forced expression of the Ebf1 targets c-Myb or Bcl-xL. In mature B cells, Ebf1 deficiency interferes with the BAFF-R and BCR-dependent Akt signaling pathways, as well as with germinal center formation and class switch recombination. Genome-wide analyses of Ebf1 binding and Ebf1-mediated gene expression in mature B cells and comparison with reported data sets in pro-B cells provide insight into the basis for lineage- and stage-specific functions of Ebf1.
2012-04-03 | GSE35914 | GEO
Project description:Early B cell factor 1 (EBF1) is one of the key transcription factors required for orchestrating B-cell lineage development. Although studies have shown that Ebf1 haploinsufficiency is involved in the development of leukemia, no study has been conducted that characterizes the global effect of Ebf1 heterozygosity on the proteome of pro-B lymphocytes. Here, we employ both DIA (Data Independent Acquisition) and shotgun DDA (Data Dependent Acquisition) workflows for profiling proteins that are differently expressed between Ebf1+/+ and Ebf1+/- cells. Both DDA and DIA were able to reveal the downregulation of the EBF1 transcription factor in Ebf1+/- pro-B lymphocytes. Further examination of differentially expressed proteins by DIA revealed that, similar to EBF1, the expression of other B-cell lineage regulators, such as TCF3 and Pax5, is also down-regulated in Ebf1 heterozygous cells. Functional DIA analysis of differentially expressed proteins showed that EBF1 heterozygosity resulted in the deregulation of at least 8 transcription factors involved in lymphopoiesis, and to the deregulation of key proteins playing crucial roles in survival, development and differentiation of pro-B lymphocytes.
2017-12-20 | PXD008396 | Pride
Project description:To study the function of EBF1-H240 residue, a gain-of function microarray analysis was performed by transducing Empty, Ebf1-wt and Ebf1-H240A expressing vectors into Ebf1-/- progenitor cells.
2016-11-21 | GSE87634 | GEO
Project description:Ebf1 is a key determinant of B-lymphocyte specification. In order to identify unknown transcriptional targets, endogenous Ebf1 was isolated by chromatin-IP from primary pro-B cells and the copurified DNA was hybridized to promoter tiling arrays. Ebf1 was ChIPed using a polyclonal antibody directed against an N-terminal peptide from primary pro-B cells grown in the presence of Il7. The resulting DNA was analyzed by tiling array hybridization.
2010-06-24 | E-GEOD-21469 | biostudies-arrayexpress