Multiple endocrine Neoplasia (MEN) is a rare inherited syndrome that occurs due to the RET (rearranged in trans infection) germline mutation. MEN 2a is more frequent followed by FTC and MEN 2B occurs less frequently. In this case report, we present a case of a 31-year-old female who presented with neck swelling and hypertension and was diagnosed with bilateral pheochromocytomas and medullary carcinoma of the thyroid.
View Article and Find Full Text PDFBackground: Diabetic cardiomyopathy (DCM) is a leading cause of death in diabetic patients. Hyperglycemic myocardial microenvironment significantly alters chromatin architecture and the transcriptome, resulting in aberrant activation of signaling pathways in a diabetic heart. Epigenetic marks play vital roles in transcriptional reprogramming during the development of DCM.
View Article and Find Full Text PDFA pair of Down syndrome (DS) human iPSCs (hiPSCs) and isogenic euploid hiPSCs generated by using an integration-free Sendai viral vector system showed trisomy 21 (47; XY) and typical (46; XY) karyotype respectively. Pluripotency of both hiPSC lines was confirmed by pluripotency marker expression and three germ layer differentiation potentials.
View Article and Find Full Text PDFImpaired neurogenesis in Down syndrome (DS) is characterized by reduced neurons, increased glial cells, and delayed cortical lamination. However, the underlying cause for impaired neurogenesis in DS is not clear. Using both human and mouse iPSCs, we demonstrate that DS impaired neurogenesis is due to biphasic cell cycle dysregulation during the generation of neural progenitors from iPSCs named the "neurogenic stage" of neurogenesis.
View Article and Find Full Text PDFHuman mouse chimeric models are valuable tools to develop in-vivo disease models. However, in-vivo detection of human cells limits their analysis. To facilitate in-vivo modeling of Down syndrome (DS), we generated a stable AAVS1-EGFP isogenic pair of DS human iPSCs by zinc finger mediated genetic engineering of the AAVS1 locus.
View Article and Find Full Text PDFHuman-induced pluripotent stem cells (hiPSCs) clones NSi001-A, NSi001-B, and NSi001-C were generated from a female individual of Indian origin having Robertsonian translocation down syndrome (DS) by reprogramming peripheral blood mononuclear cells (PBMCs) using integration-free Sendai viral vectors. The established hiPSCs clones had karyotype similar to the patient sample with Robertsonian translocation [46, XX rob (14;21)], normal ES-like morphology, expression of pluripotency markers, and potential for three germ layer differentiation, i.e.
View Article and Find Full Text PDFZygotic gene expression programs control cell differentiation in vertebrate development. In Xenopus, these programs are initiated by local induction of regulatory genes through maternal signaling activities in the wake of zygotic genome activation (ZGA) at the midblastula transition (MBT). These programs lay down the vertebrate body plan through gastrulation and neurulation, and are accompanied by massive changes in chromatin structure, which increasingly constrain cellular plasticity.
View Article and Find Full Text PDFIn Down syndrome (DS) or trisomy of chromosome 21, the β-amyloid (Aβ) peptide product of the amyloid precursor protein (APP) is present in excess. Evidence points to increased APP gene dose and Aβ as playing a critical role in cognitive difficulties experienced by people with DS. Particularly, Aβ is linked to the late-life emergence of dementia as associated with neuropathological markers of Alzheimer's disease (AD).
View Article and Find Full Text PDFRecently, in studies examining fibroblasts obtained from the tissues of one set of monozygotic twins (i.e. fetuses derived from the same egg) discordant for trisomy 21 (Down syndrome; DS), Letourneau et al.
View Article and Find Full Text PDFBiores Open Access
February 2014
BAF chromatin remodeling complexes containing the BRG1 protein have been shown to be not only essential for early embryonic development, but also paramount in enhancing the efficiency of reprogramming somatic cells to pluripotency mediated by four transcription factors. To investigate the role of BRG1 in regulating pluripotency, we found that Oct4 and Nanog levels were increased immediately after BRG1 knockdown. While Nanog levels remained elevated over the investigated time period, Oct4 levels decreased at later time points.
View Article and Find Full Text PDFOct4A is a core component of the regulatory network of pluripotent cells, and by itself can reprogram neural stem cells into pluripotent cells in mice and humans. However, its role in defining totipotency and inducing pluripotency during embryonic development is still unclear. We genetically eliminated maternal Oct4A using a Cre/loxP approach in mouse and found that the establishment of totipotency was not affected, as shown by the generation of live pups.
View Article and Find Full Text PDFUnlabelled: Death receptor-mediated apoptosis of hepatocytes contributes to hepatitis and fulminant liver failure. MicroRNAs (miRNAs), 19-25 nucleotide-long noncoding RNAs, have been implicated in the posttranscriptional regulation of the various apoptotic pathways. Here we report that global loss of miRNAs in hepatic cells leads to increased cell death in a model of FAS/CD95 receptor-induced apoptosis.
View Article and Find Full Text PDFReprogramming of somatic cells achieved by combination of the four transcription factors Oct4, Sox2, Klf4, and c-Myc has very low efficiency. To increase the reprogramming efficiency and better understand the process, we sought to identify factors that mediate reprogramming with higher efficiency. We established an assay to screen nuclear fractions from extracts of pluripotent mouse cells based on Oct4 reactivation.
View Article and Find Full Text PDFDuring the development of multicellular organisms, both transient and stable gene expression patterns have to be established in a precisely orchestrated sequence. Evidence from diverse model organisms indicates that this epigenetic program involves not only transcription factors, but also the local structure, composition, and modification of chromatin, which define and maintain the accessibility and transcriptional competence of the nucleosomal DNA template. A paradigm for the interdependence of development and chromatin is constituted by the mechanisms controlling the specification and differentiation of the skeletal muscle cell lineage in vertebrates, which is the topic of this review.
View Article and Find Full Text PDF