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A Novel EBF2 Nonsense Variant Drives Adipose Tissue Fibrosis and Dysfunction in Partial Lipodystrophy Syndrome

ABSTRACT: Heterozygous Ebf2 p.E165X knock-in (KI) mice exhibited restricted adipogenesis and excess extracellular matrix (ECM) deposition during post-weaning AT expansion and high-fat-diet (HFD)-induced obesity.

ORGANISM(S): Mus musculus

PROVIDER: GSE288829 | GEO | 2025/02/17

REPOSITORIES: GEO

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A Novel EBF2 Nonsense Variant Drives Adipose Tissue Fibrosis and Dysfunction in Partial Lipodystrophy Syndrome

Project description:In vitro disease modeling of an erly B cell factor 2 (EBF2) nonsense variant (EBF2 8:26033143 C>A, c.493G>T, p.E165X) demonstrates that the EBF2 variant impairs adipogenesis causing excess accumulation of extracelluar matrix protein and inflammatory myeloid cells.

2025-02-17 | GSE288824 | GEO

A Novel EBF2 Nonsense Variant Drives Adipose Tissue Fibrosis and Dysfunction in Partial Lipodystrophy Syndrome

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A Novel EBF2 Nonsense Variant Drives Adipose Tissue Fibrosis and Dysfunction in Partial Lipodystrophy Syndrome

Project description:A Novel EBF2 Nonsense Variant Drives Adipose Tissue Fibrosis and Dysfunction in Partial Lipodystrophy Syndrome

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Expression profiling of Ebf2- and Ebf2- stromal cells in mouse bone marrow

Project description:To identify the true molecular features of the Ebf2+ cells, we performed microarray analysis of freshly sorted CD45-TER119-Ebf2+ and Ebf2- cells. This allowed for the detection of 1968 genes that were 2-fold differentially expressed in Ebf2+ and Ebf2- cells. Among these, 1075 genes were upregulated and 893 genes including Ebf2, were downregulated in the Ebf2- as compared to the Ebf2+ cells. These include Nov, Fmod, Ndn, Dcn, Ctgf, Angiopoietin like-1(Angptl1), Fn1 and Jag1, some of which has been reported to be expressed in culture-selected MSCs. Furthermore, consistent with antigen expression analysis by FACS, the Ebf2+ cells highly expressed transcripts of Pdgfra, Pdgfrb, Sca1/Ly6a, Thy1 and Itga7 and Itgav, that have been suggested to be linked to MSCs. Nestin was mainly expressed in the Ebf2+ cells whereas it was hardly detectable in the Ebf2- cells. Altogether, molecularly, the Ebf2+ cells displayed features of a MSC. Ebf2 expression is not restricted to committed osteoblast progenitor cells but rather marks a multipotent mesenchymal progenitor cell population in adult mouse BM. These cells do not appear to be completely overlapping with the previous reported MSC populations. The findings provide new insights into the in vivo cellular identity and molecular properties of BM mesenchymal stem and progenitor cells. RNA was extracted from 1,000 or 2000 purified adult bone marrow cells using the RNAeasy microkit. RNA was labeled and amplified by dual amplification and hybridized to Affymetrix microarray MOE430_2, according to AffymetrixTM GeneChip Expression Analysis Technical Manual. Probe level expression values were calculated using the RMA algorithm.

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Expression profiling of Ebf2- and Ebf2- stromal cells in mouse bone marrow

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Ebf2-GFP in IEO cells

Project description:Comparison of Ebf2-expressing bone marrow mesenchymal cells from Ebf2-GFP heterozgous and Ebf2-GFP homozygous (=knock-out) mice

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Gene expression comparison between Ebf2 -/- and WT P2 Sciatic nerves

Project description:Ebf genes regulate differentiation of several cell type. Ebf2 is expressed in Schwann cells and Ebf2-/- mice show among other phenotypical abnormalities a delay in the onset of myelination associated to a decreased expression of genes regulating myelination. In addition at one month of age Ebf2-/- mice show decreased motor conduction velocity and morphological alteration in sciatic nerves. Ebf2 target genes are unknown. To identify Ebf2 target genes with a role in myelination, we compared the expression profiles of sciatic nerves isolated from P2 Wt and Ebf2-/- mice by microarray analysis. We used microarray to find Ebf2 candidate target genes by comparing gene expression of Ebf2-/- sciatic nerve and wt nerves 2 days postnatally (P2) a time point in which Ebf2-/- pups present a delay in the onset of myelination.

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Ebf2 Knockout Brown Adipose Tissue [RNA-Seq]

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EBF2-regulated epigenome in brown adipose tissue [ChIP-Seq]

Project description:EBF2 activates the expression of brown fat-selective genes in adipocytes, but whether EBF2 regulates these genes via direct binding was unknown. To address this question, we analyzed the genome-wide binding profile of EBF2 in BAT using chromatin immunoprecipitation followed by deep sequencing (ChIP-seq). To determine if EBF2 is required for the activity of lineage-specific enhancers, we examined the levels of PPARγ, RNA Polymerase II (Pol II), and H3K27ac at brown fat-specific genes in wildtype (WT) and Ebf2 KO BAT.

2017-04-27 | GSE97114 | GEO

Ebf2 is a selective marker of brown and beige adipogenic precursor cells (Microarray)

Project description:Brown adipocytes, muscle and dorsal dermis descend from precursor cells in the dermomyotome, but the factors that regulate commitment to the brown adipose lineage are unknown. Here, we prospectively isolated and determined the molecular profile of embryonic brown preadipose cells. Brown adipogenic precursor activity in embryos was confined to PdgfrÎ±+, Myf5Cre-lineage-marked cells. RNAseq analysis identified Early B Cell Factor-2 (Ebf2) as one of the most selectively expressed genes in this cell fraction. Importantly, Ebf2-expressing cells purified from Ebf2-GFP embryos or brown fat tissue did not express myoblast or dermal cell markers and uniformly differentiated into brown adipocytes. Interestingly, Ebf2-expressing cells from white fat tissue in adult animals differentiated into brown-like (or beige) adipocytes. Loss of Ebf2 in brown preadipose cells reduced the expression levels of brown preadipose-signature genes, whereas ectopic Ebf2-expression in myoblasts activated brown preadipose-specific genes. Altogether, these results indicate that Ebf2 specifically marks and regulates the molecular profile of brown preadipose cells. Embryonic fibroblasts, isolated from dorsal body wall of E14.5 Ebf2(GFP)/+ embryos, were further fractionated based on the expression of PDGFRÎ± and Ebf2 (GFP). Affymetrix microarray analysis was prefromed,to compare the gene expression between PDGFRÎ±+ Ebf2(GFP)- and PDGFRÎ±+ Ebf2(GFP)+ cells.

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