Microarray analysis of Mef2c deficient and control bone marrow pro-B cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE63997 | GEO | 2016/07/12
SECONDARY ACCESSION(S): PRJNA269751
REPOSITORIES: GEO
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Project description:Gene expression of mice bone marrow pre-B cells from both control and Vav-Cre Mef2cfl/fl mice (9 months old) We used these microarrays to identify the function of MEF2C in BM B lymphoid progenitors
2016-07-12 | GSE63996 | GEO
Project description:6-plex TMT LC-MSMS quantification of proteins in myeloid progenitors (Lineage- Sca1- Kit+ cells) isolated from the bone marrow of 8-12 week old male and female control and Elp3-deficient (Elp3fl/fl vav-iCreT/+) mice. Biological triplicates of each genotype were analyzed, each consisting of 1.10e6 cells from pools of 12-14 control (Elp3fl/fl) or 26-38 (Elp3-deficient) male and female mice.
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Project description:Despite recent advances in the identification of lymphoid-restricted progenitors, the transcription factors essential for their generation remain to be identified. Here we describe an unexpected role for the myeloid oncogene Mef2c in multipotent progenitors (MPPs), where it is required for pan-lymphoid differentiation. Mef2c deficiency was associated with profound defects in B, T, NK cell and common lymphoid progenitor production and an enhanced myeloid output. Mef2c deficiency in MPPs leads to downregulation of several key lymphoid regulators and the upregulation of the myeloid factor C/EBPa. Our studies also show that Mef2c is a critical transcriptional target of PU.1 during lymphopoiesis. Thus, Mef2c is a crucial component of the transcriptional network that regulates lymphoid specification and cell fate choice in MPPs.
2008-11-21 | GSE13686 | GEO
Project description:Human bone marrow mesenchymal stromal cells (BM-MSC) could be committed toward a functional lymphoid-like stroma by a combination of TNFalpha (TNF) and Lymphotoxin alpha1/beta2 (LT) (Amé-Thomas et al Blood 2007). Bone marrow and lymph node stromal cells support FL malignant cell recruitment and growth in particular after comittment to a lymphoid-like differentiation in vitro. In addition, more than 70% of FL patients exhibit a bone marrow involvment at diagnosis. We delineate using Affymetrix U133+2.0 microarrays the gene expression profile of BM-MSC obtained from FL patients (FL-MSC) and age-matched healthy donors (HD-MSC) in order to identify a specific FL-MSC signature. In addition, we used Affymetrix microarrays to define the gene expression signature of lymphoid-like stromal cells obtained from HD-MSC by treatment with TNF/LT in vitro. This TNF/LT signature was then used to interpret the gene expression profile of FL-MSC.
2012-01-26 | GSE35331 | GEO
Project description:The bHLH transcription factor stem cell leukemia gene (Scl) is a master regulator for hematopoiesis essential for hematopoietic specification and proper differentiation of the erythroid and megakaryocyte lineages. However, the critical downstream targets of Scl remain undefined. Here, we identified a novel Scl target gene, transcription factor myocyte enhancer factor 2 C (Mef2C) from Sclfl/fl fetal liver progenitor cell lines. Analysis of Mef2C-/- embryos showed that Mef2C, in contrast to Scl, is not essential for specification into primitive or definitive hematopoietic lineages. However, adult VavCre+Mef2Cfl/fl mice exhibited platelet defects similar to those observed in Scl deficient mice. The platelet counts were reduced, while platelet size was increased and the platelet shape and granularity was altered. Furthermore, megakaryopoiesis was severely impaired in vitro. ChIP-on-chip analysis revealed that Mef2C is directly regulated by Scl in megakaryocytic cells, but not in erythroid cells. In addition, an Scl independent requirement for Mef2C in B-lymphoid homeostasis was observed in Mef2C-deficient mice, characterized as severe age-dependent reduction of specific B cell progenitor populations reminiscent of premature aging. In summary, this work identifies Mef2C as an integral member of hematopoietic transcription factors with distinct upstream regulatory mechanisms and functional requirements in megakaryocyte and B-lymphoid lineages. Experiment Overall Design: Sclfl/fl hematopoietic progenitor lines were generated from fetal liver progenitors from E12.5 Sclfl/fl embryos9 by immortalization with Hox11 retrovirus.17 Sclfl/fl progenitor cells were cultured with IL3, and a clonal line containing cells with megakaryocyte morphology and acetylcholinesterase (AchE) activity was selected. The Sclfl/fl cell line was transduced with Cre- GFP retrovirus to generate the Scl Experiment Overall Design: Î?/Î? cell line, and the Scl Î?/Î? cell line was transduced with Scl retrovirus to re-introduce Scl expression (Scl Î?/Î? +Scl cell line). Megakaryocyte differentiation was enhanced by adding Tpo for 5 days before harvesting the cells. RNA was extracted with Trizol (Gibco BRL) and RNEasy (Qiagen) kits. Differential gene expression between Sclfl/fl, Scl Î?/Î? and Scl Î?/Î? +Scl cell lines was analyzed by Affymetrix MOE430_2 microarray in the microarray core facility at the Dana-Farber Cancer Institute.
2009-02-08 | E-GEOD-14478 | biostudies-arrayexpress
Project description:Acute myelogenous leukemia (AML) is driven by leukemic stem cells (LSC) generated by mutations that confer (or maintain) self-renewal potential coupled to an aberrant differentiation program. Using retroviral mutagenesis, we identified genes that generate LSC in collaboration with genetic disruption of the gene encoding interferon response factor 8 (Irf8), which induces a myeloproliferation in vivo. Amongst the targeted genes, we identified Mef2c, encoding a MADS transcription factor, and confirmed that over-expression induced a myelomonocytic leukemia in cooperation with Irf8 deficiency. Strikingly, several of the genes identified in our screen have been reported to be upregulated in the mixed-lineage leukemia (MLL) subtype. High MEF2C expression levels were confirmed in AML patient samples with MLL gene disruptions, prompting an investigation of the causal interplay. Using a conditional mouse strain, we demonstrated that Mef2c deficiency does not impair the establishment nor maintenance of LSC generated in vitro by MLL/ENL fusion proteins â?? however, its loss led to compromised homing and invasiveness of the tumor cells. Mef2c-dependent targets included several genes encoding matrix metalloproteinases and chemokine ligands and receptors, providing a mechanistic link to increased homing and motility. Thus an early event in LSC generation may be responsible for the aggressive nature of this leukemia subtype. Experiment Overall Design: For gene expression profiling of M/E cells, RNA was isolated from M/E-Mef2c del/- cells infected with MYs-iPAC (empty vector) or MYs-pMef2cASR after puromycin selection at three different time points, pooled, and hybridized against the Agilent Whole Mouse Genome Microarray 4x44K using the one-color service of Miltenyi. Transcript levels were verified by real-time RT-PCR using the SYBRGreen Reaction Mix (Roche Mannheim) in a Roche Light-Cycler. cDNA levels were normalized against Hprt transcript levels. Primers and amplification conditions are available upon request.
2009-08-15 | E-GEOD-17231 | biostudies-arrayexpress
Project description:We analyzed the chromatin accessibility of control and Mef2c deficient mouse BM pre-B and myeloid cells by ATAC-seq analysis.
2016-07-12 | GSE81508 | GEO
Project description:The bHLH transcription factor stem cell leukemia gene (Scl) is a master regulator for hematopoiesis essential for hematopoietic specification and proper differentiation of the erythroid and megakaryocyte lineages. However, the critical downstream targets of Scl remain undefined. Here, we identified a novel Scl target gene, transcription factor myocyte enhancer factor 2 C (Mef2C) from Sclfl/fl fetal liver progenitor cell lines. Analysis of Mef2C-/- embryos showed that Mef2C, in contrast to Scl, is not essential for specification into primitive or definitive hematopoietic lineages. However, adult VavCre+Mef2Cfl/fl mice exhibited platelet defects similar to those observed in Scl deficient mice. The platelet counts were reduced, while platelet size was increased and the platelet shape and granularity was altered. Furthermore, megakaryopoiesis was severely impaired in vitro. ChIP-on-chip analysis revealed that Mef2C is directly regulated by Scl in megakaryocytic cells, but not in erythroid cells. In addition, an Scl independent requirement for Mef2C in B-lymphoid homeostasis was observed in Mef2C-deficient mice, characterized as severe age-dependent reduction of specific B cell progenitor populations reminiscent of premature aging. In summary, this work identifies Mef2C as an integral member of hematopoietic transcription factors with distinct upstream regulatory mechanisms and functional requirements in megakaryocyte and B-lymphoid lineages.
2009-01-31 | GSE14478 | GEO
Project description:Microdeletions of the MEF2C gene are linked to a syndromic form of autism termed MEF2C haploinsufficiency syndrome (MCHS). Here, we show that MCHS-associated missense mutations cluster in the conserved DNA binding domain and disrupt MEF2C DNA binding. DNA binding-deficient global Mef2c heterozygous mice (Mef2c-Het) display numerous MCHS-like behaviors, including autism-related behaviors, as well as deficits in cortical excitatory synaptic transmission. We find that hundreds of genes are dysregulated in Mef2c-Het cortex, including significant enrichments of autism risk and excitatory neuron genes. In addition, we observe an enrichment of upregulated microglial genes, but not due to neuroinflammation in the Mef2c-Het cortex. Importantly, conditional Mef2c heterozygosity in forebrain excitatory neurons reproduces a subset of the Mef2c-Het phenotypes, while conditional Mef2c heterozygosity in microglia reproduces social deficits and repetitive behavior. Together our findings suggest that MEF2C regulates typical brain development and function through multiple cell types, including excitatory neuronal and neuroimmune populations.
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Project description:Analysis of differential gene expression profiles in VAV1-/- versus VAV+/+ BM-macrophages , respectively. A distinct expression profile in VAV1-/- versus VAV1+/+ (wild-type) BM-macrophages allows to resolve molecular mechanisms.
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