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Parental origin-dependent expression of the imprinted genes is essential for mammalian development. Zfp57 maintains genomic imprinting in mouse embryos and ES cells. To examine the allelic expression patterns of the imprinted genes in ES cells, we obtained multiple hybrid ES clones that were directly derived from the blastocysts generated from the cross between mice on two different genetic backgrounds. The blastocyst-derived ES clones displayed largely intact DNA methylation imprint at the tested imprinted regions. These hybrid ES clones will be useful for future studies to examine the allelic expression of the imprinted genes in ES cells and their differentiated progeny.
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http://dx.doi.org/10.1016/j.scr.2016.01.017 | DOI Listing |
Stem Cell Rev Rep
September 2025
Stem Cells and Metabolism Research Program (STEMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, 00014, Finland.
Mutations in Delta Like Non-Canonical Notch Ligand 1 (DLK1), a paternally expressed imprinted gene, underlie central precocious puberty (CPP), yet the mechanism remains unclear. To test the hypothesis that DLK1 plays a role in gonadotropin releasing hormone (GnRH) neuron ontogeny, 75 base pairs were deleted in both alleles of DLK1 exon 3 with CRISPR-Cas9 in human pluripotent stem cells (hPSCs). This line, exhibiting More than 80% loss of DLK1 protein, was differentiated into GnRH neurons by dual SMAD inhibition (dSMADi), FGF8 treatment and Notch inhibition, as previously described, however, it did not exhibit accelerated GNRH1 expression.
View Article and Find Full Text PDFIdentifying drivers of metastasis is essential for developing new treatments for patients with advanced disease. Here, we identify as a robust driver of breast cancer metastasis. Previous work established as an imprinted gene expressed by trophoblasts which are critical for vascular remodeling during placental development.
View Article and Find Full Text PDFAutosomal monoallelic gene expression and asynchronous replication between alleles are well-established features of imprinted genes and genes regulated by allelic exclusion. Inactivation/Stability Centers (I/SCs) are recently described autosomal loci that exhibit epigenetic regulation of allelic expression and replication timing, with differences that can be comparable to those observed between the active and inactive X chromosomes . Here we characterize hundreds of autosomal loci with allele-specific epigenetic regulation of replication timing and gene expression, defining them as I/SCs.
View Article and Find Full Text PDFCardiovasc Endocrinol Metab
September 2025
Biochemistry Department, Azerbaijan Medical University, Baku, Azerbaijan.
Central precocious puberty (CPP) results from premature reactivation of the hypothalamic-pituitary-gonadal axis and is increasingly recognized as a systemic condition linked to cardiometabolic health. Genetic mutations, particularly in imprinted genes such as and , are major monogenic causes of familial CPP, while rare activating variants in and highlight the pivotal role of kisspeptin signaling. Neuropeptides, including kisspeptin and neurokinin B, are central to pubertal regulation.
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