Y-chromosome clonal random expression produces mosaics in male mice
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PROVIDER: PRJNA1129861 | ENA |
REPOSITORIES: ENA
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Project description:Monoallelic expression of X-chromosome inactivation (XCI) genes produces female mosaicism, but it is unknown whether chromosome Y (chrY) mosaicism exists in males. ChrY contains some ubiquitously expressed and evolutionary conserved dosage-sensitive regulator genes, including neighbouring Kdm5d, Ddx3y, Uty, and (in mice) Eif2s3y, that have on chrX counterparts that escape XCI. Here, we have produced a transgenic mice line containing an EGFP gene between Uty and Ddx3y genes. These males have mosaic (tortoiseshell) green fluorescence in the skin, similar to females carrying one copy (hemizygous) of an X-linked EGFP transgene owing to inactivation of one chrX, and show clonal inheritance of the inactive state through cell division. The skin tortoiseshell expression of the Y-GFP indicates that the choice of which chrY remains active is stably maintained and clonally inherited. We have produced 3 Sertoli lines from Y-GFP transgenic male, and we have separated by flow cytometry size homogeneous GFP-positive and GFP-negative cells. To analyse the transcriptomic profile and evaluate whether genes from chrY follow the same EGFP expression pattern and explore the regulatory mechanism of the chrY we performed RNA-seq. The results indicate that GFP-positive and GFP-negative cells have considerable differences in their expression levels at chrY, chrX and autosomal chromosomes. Concretely, 18 chrY genes show under expression in GFP-negative cells, including Ddx3y, Zfy1, Zfy2, Usp9y, Uba1y and 10 genes from the Rbmy family. Moreover, the differences in expression observed brings out the influence of chromosome Y expression on the expression of the rest of the autosomal genes.
2025-02-05 | GSE271104 | GEO
Project description:Genetic mosaics were induced in 3rd instar larvae by heatshock to generate H3K27R mutants, Su(z)12 mutants or E(z) mutants
2022-05-31 | E-MTAB-10762 | biostudies-arrayexpress
Project description:Microglia constitute a highly specialized network of tissue resident immune cells that is important for the control of tissue homeostasis and the resolution of virtually all diseases of the central nervous system (CNS). However, how this dissemination is established and maintained in vivo and its kinetics of these processes are poorly understood. Here we established a new multicolor fluorescence fate mapping system to monitor microglia dynamics during steady state and disease. Our findings that microglia establish a stable network over time albeit with regional differences and remarkably high turnover rates challenge their postulated longevity. Microglia self-renewal constitutes a random process without evidence of defined progenitor cells. Under pathological conditions this randomness shifts to clonal microglia expansion that is finally resolved by both cell apoptosis and egression for re-establishment of the stable microglia network. Our data reveal new insights on how microglia ensure their complex distribution throughout the healthy and diseased CNS .
2017-03-27 | GSE79252 | GEO
Project description:To determine sensitivity of a custom 8x60k aCGH design for mosaicism of SNCA gains, a peripheral blood lymphocyte (PBL) DNA sample with a known heterozygous duplication (CN 3, or 50% increase in SNCA) was diluted with a control (wild type, wt) sample (CN 2, screened by MLPA) to create "artifical mosaics" (CN 2.4, 2.3, 2,25, 2.2, 2.15, 2.1). Dilutions, as well as the undiluted heterozygous sample, and the control, were tested, hybridised with Agilent reference DNA.
2016-02-01 | GSE71355 | GEO
Project description:Random monoallelic expression is defined by the allele-specific expression of genes, and by the fact that for an individual cell this monoallelic expression is neither obligate nor necessarily coordinated with the allelic expression in other cells. In order to find novel examples of random monoallelic expression in mouse, we did a transcriptome-wide survey of allele-specific gene expression in two different immortalized cell types. Lymphoblast cell lines and fibroblast cell lines were established (both clonal and nonclonal) and were used as a source of both nuclear RNA and genomic DNA. These samples were assessed for allele-specific gene expression using a custom-designed Mouse SNP Chip. A large number of genes (over 10% of those that were assessed in lymphoblast clones) displayed random monoallelic expression.
2012-02-10 | GSE35678 | GEO
Project description:To investigate expression changes of the KO vs. control livers under 3 months of Western Diet. We then performed mRNA seq analysis on MOSAICS based single-gene whole-liver KO samples and control samples
2024-09-01 | GSE212916 | GEO
Project description:Random monoallelic expression is defined by the allele-specific expression of genes, and by the fact that for an individual cell this monoallelic expression is neither obligate nor necessarily coordinated with the allelic expression in other cells. In order to find novel examples of random monoallelic expression in mouse, we did a transcriptome-wide survey of allele-specific gene expression in two different immortalized cell types. Lymphoblast cell lines and fibroblast cell lines were established (both clonal and nonclonal) and were used as a source of both nuclear RNA and genomic DNA. These samples were assessed for allele-specific gene expression using a custom-designed Mouse SNP Chip. A large number of genes (over 10% of those that were assessed in lymphoblast clones) displayed random monoallelic expression. For each cell line, two replicate samples of ds-cDNA were assessed for monoallelic expression, while genomic DNA was assessed as a control for possible LOH events. Nonclonal samples were used as controls for cis-acting allelic bias.
2012-02-10 | E-GEOD-35678 | biostudies-arrayexpress
Project description:To ensure dosage compensation between the sexes, one randomly chosen X chromosome is silenced in each female cell in the process of X-chromosome inactivation (XCI). XCI is a model for cellular decision making and epigenetic gene regulation. The random cell-autonomous nature of XCI however has so far prevented its chromosome-wide investigation in its endogenous context without genetic perturbation. Here we use allele-specific single-cell RNA-sequencing to assess the onset of random XCI with high temporal resolution in differentiating mouse embryonic stem cells, and develop dedicated analysis approaches. We find that XCI is initiated on both chromosomes in a subset of cells, but reverted to the final mono-allelic state once gene silencing is established. By exploiting the heterogeneity of XCI onset, we identify Nanog as its main trigger and discover additional genes that might control upregulation of Xist, the master regulator of XCI. Finally, we show that genetic variation between different mouse strains modulates the XCI process at multiple levels, and validate these findings through an orthogonal experimental approach. We thus draw a detailed picture of how XCI is initiated and the experimental and computational strategies we have developed here will now allow us to profile random XCI in more physiological contexts, including primary human cells in vivo.
2020-05-22 | GSE151009 | GEO
Project description:Dynamic Erasure of Random X-Chromosome Inactivation during iPSC Reprogramming
| PRJNA521357 | ENA
Project description:The various types of retinal neurons are each positioned at their respective depths within the retina where they are believed to be assembled as orderly mosaics, in which like-type neurons minimize proximity to one another. Two common statistical analyses for assessing the spatial properties of retinal mosaics include the nearest neighbor analysis, from which an index of their "regularity" is commonly calculated, and the density recovery profile derived from autocorrelation analysis, revealing the presence of an exclusion zone indicative of anti-clustering. While each of the spatial statistics derived from these analyses, the regularity index and the effective radius, can be useful in characterizing such properties of orderly retinal mosaics, they are rarely sufficient for conveying the natural variation in the self-spacing behavior of different types of retinal neurons and the extent to which that behavior generates uniform intercellular spacing across the mosaic. We consider the strengths and limitations of these and other spatial statistical analyses for assessing the patterning in retinal mosaics, highlighting a number of misconceptions and their frequent misuse. Rather than being diagnostic criteria for determining simply whether a population is "regular," they should be treated as descriptive statistics that convey variation in the factors that influence neuronal positioning. We subsequently apply multiple spatial statistics to the analysis of eight different mosaics in the mouse retina, demonstrating conspicuous variability in the degree of patterning present, from essentially random to notably regular. This variability in patterning has both a developmental as well as a functional significance, reflecting the rules governing the positioning of different types of neurons as the architecture of the retina is assembled, and the distinct mechanisms by which they regulate dendritic growth to generate their characteristic coverage and connectivity.
| S-EPMC7368823 | biostudies-literature