Impaired nutrient absorption and alterations in gut microbiome contribute to reduced postnatal growth in Zeb2+/- mice
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PROVIDER: PRJNA1136547 | ENA |
REPOSITORIES: ENA
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Project description:As a member of the ZFH1 family of two-handed zinc finger/homeodomain transcription factors, ZEB2 plays a pivotal role in regulating cell differentiation and early fetal development. Loss-of-function mutations lead to Mowat-Wilson syndrome (MWS), a rare genetic disorder associated with significant growth retardation for reasons that remain unknown. In this study, we established a global Zeb2 heterozygous knockout mouse model and observed reduced postnatal growth closely resembling the delayed physical development seen in patients with MWS. Both the daily and cumulative food intake of Zeb2+/- mice were significantly lower compared to their wild-type counterparts. This was accompanied by lower fat mass, reduced weights of epididymal,perigonadal, and mesenteric white adipose tissues, and reduced bone mass. H&E staining revealed a significant reduction in villi height. Downregulated genes in duodenum were enriched in fat and protein digestion and absorption pathways.Additionally, we observed a shift in the gut microbiome of Zeb2+/- mice, with multiple microbiota showing significant and positive correlations with postnatal growth-related indicators. Our findings underscore the critical role of the Zeb2 gene in physical development, its direct regulation of small intestine function, and its influence on the composition of the gut microbiome. The globally Zeb2 heterozygous knockout mouse model we established also provides a robust platform for gaining deeper insights into the physiological and pathophysiological impacts on various organs affected by MWS.
2025-08-27 | GSE272386 | GEO
Project description:infarct size and subsequent deterioration in function. The identification of factors that enhance cardiac repair by the restoration of the vascular network is, therefore, of great significance. Here, we show that the transcription factor Zinc finger E-box-binding homeobox 2 (ZEB2) is increased in stressed cardiomyocytes and induces a cardioprotective cross-talk between cardiomyocytes and endothelial cells to enhance angiogenesis after ischemia. Single-cell sequencing indicates ZEB2 to be enriched in injured cardiomyocytes. Cardiomyocyte-specific deletion of ZEB2 results in impaired cardiac contractility and infarct healing post-myocardial infarction (post-MI), while cardiomyocyte-specific ZEB2 overexpression improves cardiomyocyte survival and cardiac function. We identified Thymosin 4 (TMSB4) and Prothymosin (PTMA) as main paracrine factors released from cardiomyocytes to stimulate angiogenesis by enhancing endothelial cell migration, and whose regulation is validated in our in vivo models. Therapeutic delivery of ZEB2 to cardiomyocytes in the infarcted heart induces the expression of TMSB4 and PTMA, which enhances angiogenesis and prevents cardiac dysfunction. These findings reveal ZEB2 as a beneficial factor during ischemic injury, which may hold promise for the identification of new therapies.
2021-03-23 | PXD022212 | Pride
Project description:Study of loss of ZEB2 in breast cancer cells in vitro and in vivo: gene expression and phenotypic switch to more benign behavior of the cancer cells. Morphological, functional and gene microarray analysis following ZEB2 knockdown in MDAMB231 cells reveals gain of epithelial differentiation, reduction of migration, invasion and metastatic capability. The measurement of ZEB2 transcriptional activity in tumor cells efficiently predicts the probability of breast cancer patient survival. Global gene expression profiles were measured using Affymetrix U133 plus2 microarrays in MDAMB231 cells (control and ZEB2 shRNA and siRNA knockdown cells on plastic)
2016-03-15 | E-GEOD-27966 | biostudies-arrayexpress
Project description:Intestinal Fork Head Regulates Nutrient Absorption and Promotes Longevity
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Project description:14537 epithelial cells from adult human ileum, colon and rectum are performed single-cell transcriptome analysis, cell types and signature genes are presented, so as new representative genes. Bases on the gene expression pattern, difference of cell types, signaling changes, absorption funciton, inmmunity and hormone activity are analyzed. In addition, species diversity is briefly performed by analysis of human and mouse ileum single-cell database.
2019-10-21 | GSE125970 | GEO
Project description:The multi-domain transcription factor ZEB2 controls embryonic and adult cell fate decisions and maturation in many stem/progenitor cell types. Defects in these processes in specific cell types underlie Mowat-Wilson syndrome (MOWS), which is caused by ZEB2 haplo-insufficiency. Human ZEB2, like mouse Zeb2, is located on chromosome 2 downstream of an approximately 3.5 Mb-long gene-desert, lacking any protein-coding gene sequence. Using temporal high-resolution Targeted Chromatin Capture (T2C), we show major chromatin structural changes based on mapping in-cis proximities between the ZEB2 gene promoter and this gene desert during neural differentiation of induced pluripotent cells (iPSCs), including at early neuroprogenitor cell (NPC)/rosette state, where ZEB2 mRNA levels increase significantly. Combining T2C with histone-3 acetylation mapping, we identified three novel candidate enhancers about 500 kb upstream of the ZEB2 transcription start site (TSS). Functional luciferase-based assays in heterologous cells and NPCs reveal co-operation between these three enhancers. This study is the first to document in-cis regulatory elements (REs) located in ZEB2’s gene desert. The results further show the usability of T2C for future studies of ZEB2 REs in differentiation and maturation of relevant cell types, and the molecular characterization of identified MOWS patients that lack mutations in ZEB2 protein-coding exons.
2020-08-03 | GSE147000 | GEO
Project description:Cerebellar circuitry is critical for balance and motor control among a wide array of functions and largely consists of granule and Purkinje neurons. Bergmann glia in the cerebellum form distinct morphological structures that facilitate granule neuron migration during development and that maintain the cerebellar organization and functional integrity. At present, molecular control of the formation and morphogenesis of Bergmann glia remains obscure. In this study, we found that Zeb2 (a.k.a. Sip1 or Zfhx1b), a Mowat-Wilson syndrome-associated transcriptional regulator, is highly restricted to Bergmann glia and is essential for their development and maturation. The mice with Zeb2 ablation in the cerebellar neural progenitor exhibit dysgenesis of cerebellar cortical lamination and locomotion defects. Deletion of Zeb2 markedly reduced Bergmann glial proliferation, differentiation and the establishment of the normal radial scaffold, disrupting migration of granule cell progenitors from external to internal granular layers. Transcriptome profiling indicated that Zeb2 regulates multiple pathways including FGF and Notch signaling as well as axonal guidance cues including Netrin G2 and Gdf10 to control Bergmann glial development. Our data reveal that Zeb2 acts as a transcriptional integrator of diverse signaling pathways to regulate the formation and morphogenesis of Bergmann glia ensuring maintenance of cerebellar integrity, suggesting that Zeb2 dysfunction in Bergmann glia might contribute to motor deficits in Mowat-Wilson syndrome.
2018-06-25 | GSE84098 | GEO
Project description:T-bet is critical for cytotoxic T lymphocyte (CTL) differentiation, but it is unclear how it operates in a graded manner in the formation of both terminal effector and memory precursor cells during infection. We find that at high concentrations T-bet induced expression of Zeb2 mRNA, which then triggered CTLs to adopt terminally differentiated states. ZEB2 and T-bet cooperate to switch on a terminal CTL differentiation program, while simultaneously repressing genes necessary for central memory CTL development. Chromatin immunoprecipitation sequencing (ChIP-seq) showed that a large proportion of these genes were bound by T-bet, and this binding was altered by ZEB2 deficiency. Furthermore, T-bet overexpression could not fully bypass ZEB2 function. Thus, the coordinated actions of T-bet and ZEB2 outline a novel genetic pathway that forces commitment of CTLs to terminal differentiation, thereby restricting their memory cell potential. Splenocyte derived CD8+ T cells from C57BL/6 mice with either a wildtype (WT) (GzmB-Cre Zeb2+/+) or GzmB-Cre Zeb2-fl/fl (Zeb2-/-) backgrounds, following 8 days post infection with LCMV-Armstrong, were subsetted into KLRG1-hi/IL-7R-lo populations (terminal effectors, TE) or KLRG1-lo/IL-7R-hi (memory precursors, MP) populations. Four experimental groups, each with 3 samples, comprised of TE+WT, MP+WT, TE+ZEB2-/-, and MP+ZEB2-/-, were profiled for gene expression utilizing a polyA RNA prep and hybridized to the Illumina microarray platform IlluminaWG-v2.0.
2015-09-15 | E-GEOD-72408 | biostudies-arrayexpress
Project description:To elucidate the direct targets of ZEB2 in ABCs, we performed high-throughput sequencing of regulome by ATAC-seq, CUT & Tag, and CUT & RUN, leading to the identification the accessible sites with ZEB2 binding. Among the genes differentially expressed by Zeb2 deficiency, we found 33 candidate target genes of ZEB2, with 22 repressed and 11 activated by ZEB2. The critical transcription factor Mef2b, essential for GC development, was repressed by ZEB2. This direct regulation was mapped to a conserved region about 20kb downstream of Mef2b's exon I TSS, enriched with enhancer-associated features in both human and mouse.
2023-12-31 | GSE242607 | GEO
Project description:Expression data from WT cDC1s, Zeb2 KO cDC1s, Nfil3 Zeb2 DKO cDC1s and Zeb2 Id2 DKO cDC1s
| PRJNA509887 | ENA